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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
NASA NTRS1973

Prodromal disease: Immune responses of the host macrophage system to humoral factors

A composite is presented of nine studies, each yielding information contributing toward an understanding of methods designed to detect disease during the prodromal stages. The data further point to new areas of study that might be useful in early diagnoses. Five of the none experiments were done in mice. Four of these involved acute infectious disease states and one involved a chronic autoimmune type disease. Of the numerous perimeters studied of the acute diseases, the uptake of H3- thymidine by peripheral blood lymphocytes appeared to yield the earliest indication of disease. This test was not useful in studying the chronic disease state. Four of the nine studies involved application of diagnostic technics to human disease. A normal baseline for H3-thymidine incorporation by human lymphocytes was determined. A subject with severe combined immunodeficiency disease was studied. A human volunteer study was done using Influenza A live attenuated vaccine. Finally, a human volunteer study of subjects infected with Influenza A was done.

Criswell, B. S.↗
NASA NTRS1996

Cytokines and macrophage function in humans - role of stress

We have begun this study to commence the determination of the role of mild chronic stress in the effects of space flight on macrophage/monocyte function, a component of the immune response. Medical students undergoing regular periods of stress and relaxation have been shown to be an excellent model for determining the effects of stress on immune responses. We have begun using this model using the macrophage/monocyte as model leukocyte. The monocyte/macrophage plays a central role in immunoregulation. The studies to be included in this three year project are the effects of stress on: (1) interactions of monocytes with microbes, (2) monocyte production of cytokines, (3) monocyte phagocytosis and activity, and (4) monocyte expression of cell surface antigens important in immune responses. Stress hormone levels will also be carried out to determine if there is a correlation between stress effects on immune responses and hormonal levels. Psychological testing to insure subjects are actually stressed or relaxed at the time of testing will also be carried out. The results obtained from the proposed studies should be comparable with space flight studies with whole animals and isolated cell cultures. When complete this study should allow the commencement of the establishment of the role of stress as one compartment of the induction of immune alterations by space flight.

Sonnenfeld, Gerald↗
NASA NTRS1994

Differential RNA regulation by staphylococcal enterotoxins A and B in murine macrophages

Staphylococcal enterotoxin A (SEA) is significantly better than enterotoxin B (SEB) in activating tumor necrosis factor (TNF) secretion by B6MP102 cells. Both toxins bound to B6MP102 cells; however, SEB competed less effectively with SEA than SEA competed with SEB. This suggested that receptors unique to SEA were present on B6MP102 cells. Signal transduction occurred in response to both toxins. Within 30 s after addition, SEA and SEB significantly increased the F-actin concentration in B6MP102 cells. However, only SEA induced increased TNF mRNA levels. B6MP102 cells incubated with interferon-gamma and SEB secreted TNF. However, enhanced mRNA expression was delayed and the concentration of TNF secreted was less than that of B6MP102 cells stimulated with SEA. Although these data suggest that receptors unique to SEA are present on B6MP102 cells, they also indicate that staphylococcal enterotoxins differentially regulate TNF at the RNA level, perhaps because of differences in binding to the plasma membrane.

NASA Discipline Cell Biology↗
DOE OSTI2022

Single-cell RNA-Seq reveals changes in immune landscape in post-traumatic osteoarthritis

Osteoarthritis (OA) is the most common joint disease, affecting over 300 million people world-wide. Accumulating evidence attests to the important roles of the immune system in OA pathogenesis. Understanding the role of various immune cells in joint degeneration or joint repair after injury is vital for improving therapeutic strategies for treating OA. Post-traumatic osteoarthritis (PTOA) develops in ~50% of individuals who have experienced an articular trauma like an anterior cruciate ligament (ACL) rupture. Here, using the high resolution of single-cell RNA sequencing, we delineated the temporal dynamics of immune cell accumulation in the mouse knee joint after ACL rupture. Our study identified multiple immune cell types in the joint including neutrophils, monocytes, macrophages, B cells, T cells, NK cells and dendritic cells. Monocytes and macrophage populations showed the most dramatic changes after injury. Further characterization of monocytes and macrophages reveled 9 major subtypes with unique transcriptomics signatures, including a tissue resident Lyve1 hi Folr2 hi macrophage population and Trem2 hi Fcrls + recruited macrophages, both showing enrichment for phagocytic genes and growth factors such as Igf1 , Pdgfa and Pdgfc. We also identified several genes induced or repressed after ACL injury in a cell type-specific manner. This study provides new insight into PTOA-associated changes in the immune microenvironment and highlights macrophage subtypes that may play a role in joint repair after injury.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1995

The Effects of Rm-CSF and Ril-6 Therapy on Immunosuppressed Antiorthostatically Suspended Mice

Antiorthostatically suspended mice had suppressed macrophage development in both unloaded and loaded bones, indicating a systemic effect. Bone marrow cells from those mice secreted less macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) than did control mice. Because M-CSF and IL-6 are important to bone marrow macrophage maturation, we formulated the hypothesis that suppressed macrophage development occurred as a result of the depressed levels of either M-CSF or IL-6. To test the hypothesis, mice were administered recombinant M-CSF or IL-6 intraperitoneally. We showed that recombinant M-CSF therapy, but not recombinant IL-6 therapy, reversed the suppressive effects of orthostatic suspension on macrophage development. These data suggest that bone marrow cells that produce M-CSF are affected by antiorthostatic suspension and may contribute to the inhibited maturation of bone marrow macrophage progenitors.

Armstong, Jason W.↗
DOE OSTI2021

A Stochastic Intracellular Model of Anthrax Infection With Spore Germination Heterogeneity

We present a stochastic mathematical model of the intracellular infection dynamics of Bacillus anthracis in macrophages. Following inhalation of B. anthracis spores, these are ingested by alveolar phagocytes. Ingested spores then begin to germinate and divide intracellularly. This can lead to the eventual death of the host cell and the extracellular release of bacterial progeny. Some macrophages successfully eliminate the intracellular bacteria and will recover. Here, a stochastic birth-and-death process with catastrophe is proposed, which includes the mechanism of spore germination and maturation of B. anthracis . The resulting model is used to explore the potential for heterogeneity in the spore germination rate, with the consideration of two extreme cases for the rate distribution: continuous Gaussian and discrete Bernoulli. We make use of approximate Bayesian computation to calibrate our model using experimental measurements from in vitro infection of murine peritoneal macrophages with spores of the Sterne 34F2 strain of B. anthracis . The calibrated stochastic model allows us to compute the probability of rupture, mean time to rupture, and rupture size distribution, of a macrophage that has been infected with one spore. We also obtain the mean spore and bacterial loads over time for a population of cells, each assumed to be initially infected with a single spore. Our results support the existence of significant heterogeneity in the germination rate, with a subset of spores expected to germinate much later than the majority. Furthermore, in agreement with experimental evidence, our results suggest that most of the spores taken up by macrophages are likely to be eliminated by the host cell, but a few germinated spores may survive phagocytosis and lead to the death of the infected cell. Finally, we discuss how this stochastic modelling approach, together with dose-response data, allows us to quantify and predict individual infection risk following exposure.

59 BASIC BIOLOGICAL SCIENCES↗