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36 records · Page 2

Desert dust induces TLR signaling to trigger Th2-dominant lung allergic inflammation via a MyD88-dependent signaling pathway

Asian sand dust (ASD) is known to exacerbate asthma, although its mechanism is not yet well understood. In this study, when the effects on inflammatory response by LPS present in ASD was investigated by measuring the gene expression of cytokines and chemokines in RAW264.7 cells treated with ASD and/or polymyxin B (PMB), the ASD effects were attenuated by PMB, but not completely. When an in vitro study was performed using bone marrow-derived macrophages (BMDMs) from WT, TLR2{sup −/−}, TLR4{sup −/−}, and MyD88{sup −/−} BALB/c mice and BMDMs from WT, TLR2{sup −/−}, TLR4{sup −/−}, TLR2/4{sup −/−}, TLR7/9{sup −/−}, and MyD88{sup −/−} C57BL/6J mice, cytokine (IL-6, IL-12) production in BMDMs was higher in ASD-stimulated TLR2{sup −/−} cells than in TLR4{sup −/−} cells, whereas it was lower or undetectable in TLR2/4{sup −/−} and MyD88{sup −/−} cells. These results suggest that ASD causes cytokine production predominantly in a TLR4/MyD88-dependent pathway. When WT and TLRs 2{sup −/−}, 4{sup −/−}, and MyD88{sup −/−} BALB/c mice were intratracheally challenged with OVA and/or ASD, ASD caused exacerbation of lung eosinophilia along with Th2 cytokine and eosinophil-relevant chemokine production. Serum OVA-specific IgE and IgG1 similar to WT was observed in TLRs 2{sup −/−}, 4{sup −/−} mice, but not in MyD88{sup −/−} mice. The Th2 responses in TLR2{sup −/−} mice were attenuated remarkably by PMB. These results indicate that ASD exacerbates lung eosinophilia in a MyD88-dependent pathway. TLRs 2 and 4 signaling may be important in the increase in lung eosinophilia. Also, the TLR4 ligand LPS and TLR2 ligand like β-glucan may be strong candidates for exacerbation of lung eosinophilia. - Highlights: • ASD enhanced Th2 response in TLR2{sup −/−}, TLR4{sup −/−} and WT mice, but not in MyD88{sup −/−}. • Th2 responses in TLR2{sup −/−} mice were attenuated by LPS inhibitor polymyxin B. • TLR2 and TLR4 signaling is important in allergic lung disease aggravation by ASD. • MyD88 is the key adapter molecule in the signaling pathway for Th2 activation. • ASD-bound LPS and β-glucan may be strong candidates for the aggravating substances.

60 APPLIED LIFE SCIENCES↗

Health effects following subacute exposure to geogenic dusts from arsenic-rich sediment at the Nellis Dunes Recreation Area, Las Vegas, NV

Geogenic dust from arid environments is a possible inhalation hazard for humans, especially when using off-road vehicles that generate significant dust. This study focused on immunotoxicological and neurotoxicological effects following subacute exposure to geogenic dust generated from sediments in the Nellis Dunes Recreation Area near Las Vegas, Nevada that are particularly high in arsenic; the naturally-occurring arsenic concentrations in these surficial sediments ranged from 4.8 to 346 μg/g. Dust samples from sediments used in this study had a median diameter of 4.5 μm and also were a complex mixture of naturally-occurring metals, including aluminum, vanadium, chromium, manganese, iron, cobalt, copper, zinc, strontium, cesium, lead, uranium, and arsenic. Adult female B6C3F1 mice exposed via oropharyngeal aspiration to 0.01 to 100 mg dust/kg body weight, four times, a week apart, for 28 days, were evaluated 24 h after the last exposure. Peripheral eosinophils were increased at all concentrations, serum creatinine was dose responsively increased beginning at 1.0 mg/kg/day, and blood urea nitrogen was decreased at 10 and 100 mg/kg/day. Antigen-specific IgM responses and natural killer cell activity were dose-responsively suppressed at 0.1 mg/kg/day and above. Splenic CD4 + CD25 + T cells were decreased at 0.01, 0.1, 10, and 100 mg/kg/day. Antibodies against MBP, NF-68, and GFAP were selectively reduced. A no observed adverse effect level of 0.01 mg/kg/day and a lowest observed adverse effect level of 0.1 mg/kg/day were determined from IgM responses and natural killer cell activity, indicating that exposure to this dust, under conditions similar to our design, could affect these responses. - Highlights: • Toxicity of geogenic dust from arsenic-rich sediment in Nevada was characterized. • The geogenic dust is a mixture of many metals and crystalline silica. • Geogenic dust exposure decreased IgM antibodies and natural killer cell activity.

60 APPLIED LIFE SCIENCES↗

Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury

We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl{sub 2}) with the aim to understand the pathogenesis of the long-term sequelae of Cl{sub 2}-induced lung-injury. In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5 h up to 90 days after a single inhalation of Cl{sub 2}. A single dose of dexamethasone (10 mg/kg) was administered 1 h following Cl{sub 2}-exposure. A 15-min inhalation of 200 ppm Cl{sub 2} was non-lethal in Sprague-Dawley rats. At 24 h post exposure, Cl{sub 2}-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24 h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24 h but did not influence the AHR. Inhalation of Cl{sub 2} in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl{sub 2}-induced respiratory dysfunction. - Highlights: • Inhalation of Cl{sub 2} leads to acute lung inflammation and airway hyperreactivity. • Cl{sub 2} activates an inflammasome pathway of TGF-β induction. • Cl{sub 2} leads to a fibrotic respiratory disease. • Treatment with corticosteroids alone is insufficient to counteract acute lung injury.

60 APPLIED LIFE SCIENCES↗

Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

60 APPLIED LIFE SCIENCES↗

Plasticizer, di(2-ethylhexyl)phthalate (DEHP) enhances cockroach allergen extract-driven airway inflammation by enhancing pulmonary Th2 as well as Th17 immune responses in mice

Highlights: • DEHP enhances CE-induced airway inflammation/mucus secretion in mice. • DEHP enhances expression of costimulatory molecules on dendritic cells. • DEHP enhances expression of pro-inflammatory cytokines in dendritic cells. • DEHP down regulates expression of E-cadherin in airway epithelial cells. In recent decades, there has been a gradual increase in the prevalence of asthma. Various factors including environmental pollutants have contributed to this phenomenon. Plasticizer, di(2-ethylhexyl)phthalate (DEHP) is one of the commonest environmental pollutants due to its association with plastic products. DEHP gets released from plastic products easily leading to respiratory exposure in humans. As a consequence, DEHP is associated with allergic asthma in humans and animals. DEHP is reported to act as an adjuvant in ovalbumin-induced mouse models of asthma at high doses. However, these studies mostly looked into the role of DEHP on Th2 cytokines/eosinophilic inflammation without investigating the role of airway epithelial cells (AECs)/dendritic cells (DCs)/Th17 cells. Its adjuvant activity with natural allergens such as cockroach allergens at tolerable daily intake needs to be explored. Cockroach allergens and DEHP may be inhaled together due to their coexistence in work place as well as household environments. Therefore, effect of DEHP was assessed in cockroach allergens extract (CE)-induced mouse model of asthma. Airway inflammation, histopathology, mucus secretion, and immune responses related to Th2/Th17/DCs and AECs were assessed in mice with DEHP exposure alone and in combination with CE. Our study shows that DEHP converts CE-induced eosinophilic inflammation into mixed granulocytic inflammation by promoting Th2 as well as Th17 immune responses. This was probably due to downregulation of E-cadherin in AECs, and enhancement of costimulatory molecules (MHCII/CD86/CD40)/pro-inflammatory cytokines (IL-6/MCP-1) in DCs by DEHP. This suggests that DEHP facilitates development of mixed granulocytic airway inflammation in the presence of a natural allergen.

54 ENVIRONMENTAL SCIENCES↗

Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways

The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear. OBJECTIVES: We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. METHODS: DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics. RESULTS: Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils. CONCLUSION: The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

16S ribosomal RNA↗

Early exposure to thirdhand cigarette smoke affects body mass and the development of immunity in mice

Thirdhand smoke (THS) is the fraction of cigarette smoke that persists in indoor environments after smoking. We investigated the effects of neonatal and adult THS exposure on bodyweight and blood cell populations in C57BL/6 J mice. At the end of neonatal exposure, THS-treated male and female mice had significantly lower bodyweight than their respective control mice. However, five weeks after neonatal exposure ended, THS-treated mice weighed the same as controls. In contrast, adult THS exposure did not change bodyweight of mice. On the other hand, both neonatal and adult THS exposure had profound effects on the hematopoietic system. Fourteen weeks after neonatal THS exposure ended, eosinophil number and platelet volume were significantly higher, while hematocrit, mean cell volume, and platelet counts were significantly lower compared to control. Similarly, adult THS exposure also decreased platelet counts and increased neutrophil counts. Moreover, both neonatal and adult THS exposure caused a significant increase in percentage of B-cells and significantly decreased percentage of myeloid cells. Our results demonstrate that neonatal THS exposure decreases bodyweight and that THS exposure induces persistent changes in the hematopoietic system independent of age at exposure. These results also suggest that THS exposure may have adverse effects on human health.

59 BASIC BIOLOGICAL SCIENCES↗

Inducible epithelial resistance against acute Sendai virus infection prevents chronic asthma‐like lung disease in mice

Background and Purpose Respiratory viral infections play central roles in the initiation, exacerbation and progression of asthma in humans. An acute paramyxoviral infection in mice can cause a chronic lung disease that resembles human asthma. We sought to determine whether reduction of Sendai virus lung burden in mice by stimulating innate immunity with aerosolized Toll‐like receptor (TLR) agonists could attenuate the severity of chronic asthma‐like lung disease. Experimental Approach Mice were treated by aerosol with 1‐μM oligodeoxynucleotide (ODN) M362, an agonist of the TLR9 homodimer, and 4‐μM Pam2CSK4 (Pam2), an agonist of the TLR2/6 heterodimer, within a few days before or after Sendai virus challenge. Key Results Treatment with ODN/Pam2 caused ~75% reduction in lung Sendai virus burden 5 days after challenge. The reduction in acute lung virus burden was associated with marked reductions 49 days after viral challenge in eosinophilic and lymphocytic lung inflammation, airway mucous metaplasia, lumenal mucus occlusion and hyperresponsiveness to methacholine. Mechanistically, ODN/Pam2 treatment attenuated the chronic asthma phenotype by suppressing IL‐33 production by type 2 pneumocytes, both by reducing the severity of acute infection and by down‐regulating Type 2 (allergic) inflammation. Conclusion and Implications These data suggest that treatment of susceptible human hosts with aerosolized ODN and Pam2 at the time of a respiratory viral infection might attenuate the severity of the acute infection and reduce initiation, exacerbation and progression of asthma.

Goldblatt, David L.↗

NF-κB perturbation reveals unique immunomodulatory functions in Prx1 + fibroblasts that promote development of atopic dermatitis

Skin is composed of diverse cell populations that cooperatively maintain homeostasis. Up-regulation of the nuclear factor κB (NF-κB) pathway may lead to the development of chronic inflammatory disorders of the skin, but its role during the early events remains unclear. Here, through analysis of single-cell RNA sequencing data via iterative random forest leave one out prediction, an explainable artificial intelligence method, we identified an immunoregulatory role for a unique paired related homeobox-1 (Prx1) + fibroblast subpopulation. Disruption of Ikkb–NF-κB under homeostatic conditions in these fibroblasts paradoxically induced skin inflammation due to the overexpression of C-C motif chemokine ligand 11 (CCL11; or eotaxin-1) characterized by eosinophil infiltration and a subsequent T H 2 immune response. Because the inflammatory phenotype resembled that seen in human atopic dermatitis (AD), we examined human AD skin samples and found that human AD fibroblasts also overexpressed CCL11 and that perturbation of Ikkb–NF-κB in primary human dermal fibroblasts up-regulated CCL11. Monoclonal antibody treatment against CCL11 was effective in reducing the eosinophilia and T H 2 inflammation in a mouse model. Together, the murine model and human AD specimens point to dysregulated Prx1 + fibroblasts as a previously unrecognized etiologic factor that may contribute to the pathogenesis of AD and suggest that targeting CCL11 may be a way to treat AD-like skin lesions.

60 APPLIED LIFE SCIENCES↗

Morphological and molecular characterization of a Sarcocystis bovifelis-like sarcocyst in American beef

Abstract Background Parasites in the apicomplexan genusSarcocystisinfect cattle worldwide. Assessing the economic importance of each such parasite species requires proper diagnosis.Sarcocystiscruzi,a thin-walled species, infects virtually all cattle. The prevalence of the other thin-walled parasite,Sarcocystisheydorni, remains less well established. The remaining six species all have thick (> 3 µm) cyst walls (Sarcocystishirsuta,S.hominis,S.bovifelis,S.bovini,S.sigmoideus, andS.rommeli). Thick-walled sarcocysts often induce inflammation in striated muscles (causing bovine eosinophilic myositis), leading to condemnation of carcasses at slaughter. One of these,S.hirsuta, can be seen macroscopically and lead to condemnation of beef. TwoSarcocystisspecies,S.hominisandS.heydorni, are zoonotic. AlthoughS.hominishas been reported as prevalent in Europe, the occurrence of thick-walled species in the US remains poorly known. Here, for the first time to our knowldge, we characterize a thick-walledSarcocystisspecies from a sample of beef from a local grocery store in Maryland. By morphological and genetic criteria, it closely, but not perfectly, resembles parasites previously ascribed toS.bovifelis. Methods Beef samples were examined forSarcocystisinfection, using acid-pepsin digestion to search for bradyzoites, microscopically by compression between a glass slide and coverslip, by histology of paraffin embedded sections stained with hematoxylin and eosin, and by transmission electron microscopy (TEM). Molecular characterization was attempted employing genetic markers:18SrRNA,28SrRNA,cox1,ITS1,gapdh1,ron3, andrpoB. Results Molecular evaluation revealed 100% identity withS.bovifelis-like sarcocysts from naturally infected cattle from Germany and Argentina; although the condition of the frozen material precludes complete characterization by TEM, we noted morphological features which differed from theS.bovifelisoriginally described from experimentally infected cattle from Germany. Conclusions A novelSarcocystisspecies is described from beef from the USA but not named until further evaluation. Graphical Abstract

Parasitology↗

A Fully Human IgE Specific for CD38 as a Potential Therapy for Multiple Myeloma

Multiple myeloma (MM) is an incurable malignancy of plasma cells and the second most common hematologic malignancy in the United States. Although antibodies in clinical cancer therapy are generally of the IgG class, antibodies of the IgE class have attractive properties as cancer therapeutics, such as their high affinity for Fc receptors (FcεRs), the low serum levels of endogenous IgE allowing for less competition for FcR occupancy, and the lack of inhibitory FcRs. Importantly, the FcεRs are expressed on immune cells that elicit antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and/or antigen presentation such as mast cells, eosinophils, macrophages, and dendritic cells. We now report the development of a fully human IgE targeting human CD38 as a potential MM therapy. We targeted CD38 given its high and uniform expression on MM cells. The novel anti-CD38 IgE, expressed in mammalian cells, is properly assembled and secreted, exhibits the correct molecular weight, binds antigen and the high affinity FcεRI, and induces degranulation of FcεRI expressing cells in vitro and also in vivo in transgenic BALB/c mice expressing human FcεRIα. Moreover, the anti-CD38 IgE induces ADCC and ADCP mediated by monocytes/macrophages against human MM cells (MM.1S). Importantly, the anti-CD38 IgE also prolongs survival in a preclinical disseminated xenograft mouse model using SCID-Beige mice and human MM.1S cells when administered with human peripheral blood mononuclear cells (PBMCs) as a source of monocyte effector cells. Our results suggest that anti-CD38 IgE may be effective in humans bearing MM and other malignancies expressing CD38.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants

The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, yet we have limited information regarding the breadth of variant-specific host responses. Using primary cell cultures and the K18-hACE2 mouse, we investigated the replication, innate immune response, and pathology of closely related, clinical variants circulating during the first wave of the pandemic. Mathematical modeling of the lung viral replication of four clinical isolates showed a dichotomy between two B.1. isolates with significantly faster and slower infected cell clearance rates, respectively. While isolates induced several common immune host responses to infection, one B.1 isolate was unique in the promotion of eosinophil-associated proteins IL-5 and CCL11. Moreover, its mortality rate was significantly slower. Lung microscopic histopathology suggested further phenotypic divergence among the five isolates showing three distinct sets of phenotypes: (i) consolidation, alveolar hemorrhage, and inflammation, (ii) interstitial inflammation/septal thickening and peribronchiolar/perivascular lymphoid cells, and (iii) consolidation, alveolar involvement, and endothelial hypertrophy/margination. Together these findings show divergence in the phenotypic outcomes of these clinical isolates and reveal the potential importance of nonsynonymous mutations in nsp2 and ORF8.

60 APPLIED LIFE SCIENCES↗

Human cellular immune responsiveness following space flight

Peripheral circulating lymphocytes were separated from astronaut blood samples three times before and two times after the first four US Space Shuttle flights. The ability of the in vitro T lymphocytes to respond to Phytohemagglutinin by blastogenesis was found to be reduced for each crewmember following spaceflight. In addition, the astronauts experienced a postflight increase in neutrophils and a decrease in eosinophils. These postflight changes in leukocytes are shown to increase with subjectively-evaluated increases in the incidence of inflight stress, indicating that stress, and not hypogravity, is likely to be the major effector of these changes.

Taylor, G. R.↗

Immunological analyses of U.S. Space Shuttle crewmembers

Changes in the immunoresponsiveness of 'T' lymphocytes following space flight have been reported previously. Additional data collected before and after 11 Shuttle space flights show that absolute lymphocyte numbers, lymphocyte blastogenic capability, and eosinophil percent in the peripheral blood of crewmembers are generally depressed postflight. These responses resemble those associated with physical and emotional stress and may not be related to flight per se. Additional data from Space Shuttle flights 41B and 41D, involving 11 crewmembers, indicate a postflight decrease in cells reacting with 'B' lymphocyte and monocyte monoclonal antibody tags. Further, the loss of 'T' lymphocyte blast capability correlates with the decreased monocyte count (correlation coefficient = 0.697). This finding implies that the previously reported loss of blastogenic capability may be a function of decreased monocyte control, as noted in several nonspaceflight related studies.

Taylor, G. R.↗

NASA Rat Acoustic Tolerance Test 1994-1995: 8 kHz, 16 kHz, 32 kHz Experiments

Adult male Sprague-Dawley rats were exposed to chronic applied sound (74 to 79 dB, SPL) with octave band center frequencies of either 8, 16 or 32 kHz for up to 60 days. Control cages had ambient sound levels of about 62 dB (SPL). Groups of rats (test vs. control; N=9 per group) were euthanized after 0. 5. 14, 30, and 60 days. On each euthanasia day, objective evaluation of their physiology and behavior was performed using a Stress Assessment Battery (SAB) of measures. In addition, rat hearing was assessed using the brain stem auditory evoked potential (BAER) method after 60 days of exposure. No statistically significant differences in mean daily food use could be attributed to the presence of the applied test sound. Test rats used 5% more water than control rats. In the 8 kHz and 32 kHz tests this amount was statistically significant(P less than .05). This is a minor difference of questionable physiological significance. However, it may be an indication of a small reaction to the constant applied sound. Across all test frequencies, day 5 test rats had 6% larger spleens than control rats. No other body or organ weight differences were found to be statistically significant with respect to the application of sound. This spleen effect may be a transient adaptive process related to adaptation to the constant applied noise. No significant test effect on differential white blood cell counts could be demonstrated. One group demonstrated a low eosinophil count (16 kHz experiment, day 14 test group). However this was highly suspect. Across all test frequencies studied, day 5 test rats had 17% fewer total leukocytes than day 5 control rats. Sound exposed test rats exhibited 44% lower plasma corticosterone concentrations than did control rats. Note that the plasma corticosterone concentration was lower in the sound exposed test animals than the control animals in every instance (frequency exposure and number of days exposed).

Mele, Gary D.↗

Blood biochemical and cellular changes during a decompression procedure involving eight hours of oxygen prebreathing

Chemical and cellular parameters were measured in human subjects before and after exposure to a decompression schedule involving 8 h of oxygen prebreathing. The exposure was designed to simulate space-flight extravehicular activity (EVA) for 6 h. Several statistically significant changes in blood parameters were observed following the exposure: increases in calcium, magnesium, osmolality, low-density lipoprotein cholesterol, monocytes, and prothrombin time, and decreases in chloride, creatine phosphokinase and eosinophils. The changes, however, were small in magnitude and blood factor levels remained within normal clinical ranges. Thus, the decompression profile used in this study is not likely to result in blood changes that would pose a threat to astronauts during EVA.

Oxygen/administration & dosage↗

Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation

As upcoming exploratory missions to the Lunar surface and Mars during the Artemis Program will send both female and male crewmembers, studies identifying sex-specific effects are necessary. It is well-documented that the immune system engages different responses between females and males following exposures to infectious challenge, tumors surveillance, and autoimmune development. Yet, the immune effects of spaceflight-like exposures between the sexes are limited. Therefore, this study sought to address the effects of spaceflight-like conditions on immune differentials in female and male mice. We hypothesized that the spaceflight factor, ionizing radiation, will have sex-specific effects on immune differentials. To test this, singly-housed, 12-month old female and male wildtype (Wt) mice were exposed to acute ionizing gamma irradiation (50 cGy), followed by retro-orbital blood collections at 7-days post-irradiation. Leukocytes were analyzed by flow cytometry characterizing, granulocytes, monocytes, lymphocytes (cytotoxic/helper T cells and B cells), neutrophils, eosinophils, and NK/NKT cells. Briefly, minimal sex-specific effects were observed across the cell types listed at this time point, including changes in granulocyte and lymphocyte populations. The results revealed females displayed elevated granulocytes and reduced lymphocytes compared to their male counterparts, independent of irradiation exposure. These results suggest female mice may be more capable to produce innate inflammatory mediators but may be adaptively immune compromised. In brief, this study provides insight into the sex-specific immune risks following ionizing radiation that may be experienced during spaceflight, which is relevant for future countermeasure development.

spaceflight stressors↗

Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation

As upcoming exploratory missions to the Lunar surface and Mars during the Artemis Program will send both female and male crewmembers, studies identifying sex-specific effects are necessary. It is well-documented that the immune system engages different responses between females and males following exposures to infectious challenge, tumors surveillance, and autoimmune development. Yet, the immune effects of spaceflight-like exposures between the sexes are limited. Therefore, this study sought to address the effects of spaceflight-like conditions on immune differentials in female and male mice. We hypothesized that the spaceflight factor, ionizing radiation, will have sex-specific effects on immune differentials. To test this, singly-housed, 12-month old female and male wildtype (Wt) mice were exposed to acute ionizing gamma irradiation (50 cGy), followed by retro-orbital blood collections at 7-days post-irradiation. Leukocytes were analyzed by flow cytometry characterizing, granulocytes, monocytes, lymphocytes (cytotoxic/helper T cells and B cells), neutrophils, eosinophils, and NK/NKT cells. Briefly, minimal sex-specific effects were observed across the cell types listed at this time point, including changes in granulocyte and lymphocyte populations. The results revealed females displayed elevated granulocytes and reduced lymphocytes compared to their male counterparts, independent of irradiation exposure. These results suggest female mice may be more capable to produce innate inflammatory mediators but may be adaptively immune compromised. In brief, this study provides insight into the sex-specific immune risks following ionizing radiation that may be experienced during spaceflight, which is relevant for future countermeasure development.

spaceflight stressors↗