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

Abstract

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...

Biological effects of space radiation and development of effective countermeasures

“…Such alterations in immune function are similar to those brought about when there is increased immune activation produced by exposure to pathogen associated molecular patterns (PAMPs), such as LPS (161–166). Specific examples of this are as follows: a reduction in proinflammatory cytokine production by myeloid cells (166, 167), a reduction in antigen-specific T cell effector cytokine responses (161) and a reduction in circulating NK cells (168). The changes in responses brought about by exposure to PAMPs are known as “tolerance”, in which subsequent responses are reduced in quality and quantity, which is thought to protect the host by limiting excessive inflammation and preventing septic shock (166, 169).…”

Effects of Simulated Microgravity on Functions of Neutrophil-like HL-60 Cells

“…Parabolic flight induces an increase in PMN number and the capability of PMNs to produce hydrogen peroxide (H 2 O 2 ) in response to soluble stimuli (Kaufmann et al 2009). These works seemingly indicate that the action of microgravity has enhanced the immune response of PMNs, which is inconsistent with the reduced capability of lymphocytes (Cogoli and Tschopp 1985;Konstantinova et al 1993;Meshkov and Rykova 1995;Mills et al 2002;Mills et al 2008Mills et al , 2013, monocytes (Kaur et al 2005(Kaur et al , 2008Crucian et al 2011), NK cells (Rykova et al 1992;Konstantinova et al 1993Konstantinova et al , 1995Mehta et al 2001), and macrophages (Armstrong et al 1995;Hsieh et al 2005;Ortega et al 2012;Adrian et al 2013;Wang et al 2014Wang et al , 2015Brungs et al 2015;Paulsen et al 2015) under microgravity. The underlying mechanisms for such the difference remain unclear.…”

Monocyte Phenotype and Cytokine Production Profiles Are Dysregulated by Short-Duration Spaceflight

“…Reports of monocyte levels associated with spacefl ight have varied ( 24 , 27 , 36 ); however, the percentage of CD14 1 CD16 1 ' proinfl ammatory ' monocytes was reported to decease following spacefl ight ( 10 ). Monocyte surface density of CD14 was found to be decreased postfl ight, whereas the expression of Toll-like receptor 4 was found to be increased ( 21 ). Kaur et al investigated monocyte functional parameters immediately following shortduration spacefl ight and found that oxidative burst and phagocytic capacity were altered, as well as percentages of monocytes capable of being stimulated to produce cytokines ( 20 , 21 ).…”