Changes in neutrophil functions in astronauts

Kaur, Indreshpal; Simons, Elizabeth R.; Castro, Victoria; Ott, C. Mark; Pierson, Duane L.

doi:10.1016/j.bbi.2003.10.005

Cited by 130 publications

(120 citation statements)

References 16 publications

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“…All of these factors are known to affect many physiological parameters of the astronauts, including the immune system (12,17,20,31,32,41). Their effects include decreased functions of cells of the innate immune system, including neutrophils (14,36), monocytes (15), and NK cells (17,21). The innate immune system initiates the host defense against invading microbes by specific recognition mechanisms.…”

mentioning

confidence: 99%

Effect of Spaceflight on Ability of Monocytes To Respond to Endotoxins of Gram-Negative Bacteria

Kaur

Simons

Kapadia

et al. 2008

Clin Vaccine Immunol

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Astronauts live and work in relatively crowded, confined environments on the Space Shuttle and the International Space Station. They experience a unique set of stressors that contribute to a diminishment of many immune responses. This study investigated the ability of the shuttle crew members' monocytes to respond to gram-negative endotoxin that they could encounter during infections. Blood specimens were collected from 20 crew members and 15 control subjects 10 days before launch, 3 to 4 h after landing, and 15 days after landing and from crew members during their annual medical examination at 6 to 12 months after landing. When challenged with gram-negative endotoxin, the crew member's monocytes collected at all three time points produced lower levels of interleukin-6 (IL-6) and IL-1␤ and higher levels of IL-1ra and IL-8 compared to those of control subjects. Cytokines were assessed by measuring the number of cells positive for intracellular cytokines. These values returned to normal 6 to 12 months after landing, except for IL-1ra, which was still higher (five-to sixfold) than in controls. This phenomenon was accompanied by an increased expression of Toll-like receptor 4 and decreased expression of CD14 on the crew members' monocytes at all time points. There were also increased levels of the lipopolysaccharide binding protein in the plasma of the crew members 3 to 4 h and 15 days after landing. This study shows that spaceflight-associated factors (in-flight and preflight) modulate the response of monocytes to gram-negative endotoxins.During spaceflight, astronauts are affected by many unusual factors, such as microgravity, radiation, physical and mental stresses, and isolation. Not only is spaceflight associated with in-flight factors influencing the astronauts, but even before launch, in preparation for the mission, the astronauts experience changes in circadian rhythms, rigorous training, and stresses of anticipation factors. Additionally, confinement of the crew during flight can and has resulted in the transfer of microorganisms between crew members (13,26,27). All of these factors are known to affect many physiological parameters of the astronauts, including the immune system (12,17,20,31,32,41). Their effects include decreased functions of cells of the innate immune system, including neutrophils (14, 36), monocytes (15), and NK cells (17,21). The innate immune system initiates the host defense against invading microbes by specific recognition mechanisms. The family of Toll-like receptors (TLRs) on monocytes have been shown to be involved in innate immune recognition in response to microbial antigens (1, 6, 38), such as lipopolysaccharide (LPS), or endotoxin, a major virulence factor of gram-negative bacteria (29). Tapping et al. (39) have shown that TLR4 is the predominant signaling receptor for LPS in human blood. In blood, LPS binds to LPS binding protein (LBP), which facilitates the transfer of LPS to CD14 molecules in the CD14-TLR4-MD2 complex on the cell membrane of monocytes (11). CD14 plays a ke...

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confidence: 99%

Effect of Spaceflight on Ability of Monocytes To Respond to Endotoxins of Gram-Negative Bacteria

Kaur

Simons

Kapadia

et al. 2008

Clin Vaccine Immunol

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“…Recognition of pathogens by receptor-mediated liganding initiates a variety of signals within the phagocyte, detectable within seconds of the stimulus' binding; these signals, in turn, drive the cell towards its eventual effector functions that are intended to include ingestion and killing of the invading organism within cell phagosomes (1-7). Fluorescently labeled particles such as Dextrans (19,22), zymosan (41), Bioparticles TM (42)(43)(44), immune complexes (15)(16)(17)(18)35,41) fixed or dead cells (32) have been used to indicate phagocytosis and/or to distinguish live from dead cells, generally minutes to hours after phagocytosis was initiated. While the probes used for such studies, usually fluorescein or rhodamine derivatives, are somewhat pH sensitive below 7.1, the pH they indicate, if a quantitative evaluation is made, reflects the conditions at that time, i.e., after multiple bactericidal processes have occurred and an equilibrium of sorts has been achieved.…”

Section: Discussionmentioning

confidence: 99%

Initial cytoplasmic and phagosomal consequences of human neutrophil exposure to Staphylococcus epidermidis

2009

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Microorganisms are recognized by specific phagocyte surface receptors. Liganded receptors then signal a series of events leading to phagocytosis and destruction of the organism by oxidative, lytic, and associated processes. Some organisms, such as Mycobacterium tuberculosis (Mtb), Cryptococcus neoformans (Cf), and others, evade such destruction, surviving and sometimes multiplying within the phagosome to later cause disease. To study such evasion, we developed protocols which permit simultaneous kinetic measurement of early cytoplasmic signaling and of phagosomal pH (pH p ) and oxidative burst, on a cell-by-cell basis, of polymorphonuclear (PMN) leukocytes exposed to fluorescently labeled, nonpathogenic Staphylococcus epidermidis (Se). The availability of a new, highly sensitive pH probe, pHrodo TM , permits observation of increasing pH p . Simultaneous labeling of the organism, applicable to any phagocyte target, with a probe insensitive to pH and oxidative species, such as AlexaFluor350 TM , permits distinction between binding and functional responses to it by ratioing fluorescences. Addition of an extracellular-specific quencher (Trypan blue) permits distinction between bound and phagosome-enclosed targets, so that conditions within the closed phagosome can be studied. We found that opsonization is required for functional activation of PMN by Se, that the organism causes early alkalinization of the phagosome (in contrast to Cf which hyperacidifies it), and that extracellular Ca 21 is not required for cytoplasmic Ca 21 signaling but contributes markedly to binding of Se to PMN and to ensuant bactericidal functions. These findings lead to a new approach to the study of select organisms, like Cf and Mtb, which evade killing by manipulating the phagosomal environment. ' International Society for Advancement of CytometryKey terms calcium; pH; reactive oxygen species PHAGOCYTIC cells, such as polymorphonuclear (PMN) neutrophils and tissue macrophages (MP), are essential components of the human innate defense against infection. Phagocyte surface receptors recognize invading bacteria by a variety of mechanisms, including complement-dependent opsonization, antibody/antigen binding via Fc receptors, or pattern recognition (e.g., mannose-, scavenger-, or Toll-) receptor liganding. They then signal, via changes in intracellular cation concentrations, in transmembrane potentials, and in secondary signaling (e.g., via activation of specific phospholipases) so as to initiate a series of processes that result in phagocytosis with subsequent intraphagosomal killing and clearance of the organism [for some very recent reviews see (1-7)].Many of these signaling events occur early, within seconds of ligand-receptor binding, and have been shown to vary with the specific receptors involved (8)(9)(10)(11)(12)(13)(14). Yet, the changes initiated by these signals to generate effector functions of the cell do not become measurable by conventional methods until at least minutes later. Furthermore, responses to such stimulation...

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“…Table 3 summarizes the findings of human immunity during the Space Shuttle era (11)(12)(13)(14)(15). Establishing the medical risk associated with the many changes observed in human immunity proved difficult.…”

Section: A Latent Virus Reactivationmentioning

confidence: 99%

“…Biodegradation of critical materials can result in system failures that may endanger crews. Evidence gained during the SSP suggests that infectious diseases and allergic responses may increase on long exploration missions due to sustained immune deficiencies (11)(12)(13)(14)(15) and increased virulence of some microorganism (7)(8)(9)(10). …”

Section: Identification Of Microbiological Hazards and Risksmentioning

confidence: 99%

“…Some bacteria and fungi were shown to be more virulent as a result of spaceflight (7)(8)(9)(10). Immune studies showed decreases in innate immunity, cell mediated immunity (11)(12)(13)(14)(15), and increased latent virus reactivation (16)(17)(18)(19). The approaches taken to ensure a microbiologically safe and productive environment for astronauts to work and live, along with microbiological monitoring results, various anomalies, and results of major infectious disease related research are discussed.…”

Section: Introductionmentioning

confidence: 99%

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