Antiorthostatic Suspension Stimulates Profiles of Macrophage Activation in Mice

Abstract

The antiorthostatic suspension model simulates certain physiological effects of spaceflight. We have previously reported BDF1 mice suspended by the tail in the antiorthostatic orientation for 4 days express high levels of resistance to virulent Listeria monocytogenesinfection. In the present study, we examined whether the increased resistance to this organism correlates with profiles of macrophage activation, given the role of the macrophage in killing this pathogen in vivo. We infected BDF1 mice with a lethal dose of virulent L. monocytogenes on day 4 of antiorthostatic suspension and 24 h later constructed profiles of macrophage activation. Viable listeria could not be detected in mice suspended in the antiorthostatic orientation 24 h after infection. Flow cytometric analysis revealed the numbers of granulocytes and mononuclear phagocytes in the spleen of infected mice were not significantly altered as a result of antiorthostatic suspension. Splenocytes from antiorthostatically suspended infected mice produced increased titers of IL-1. Serum levels of neopterin, a nucleotide metabolite secreted by activated macrophages, were enhanced in mice infected during antiorthostatic suspension, but not in antiorthostatically suspended naive mice. Splenic macrophages from mice infected on day 4 of suspension produced enhanced levels of lysozyme. In contrast to the results from antiorthostatically suspended infected mice, macrophages from antiorthostatically suspended uninfected mice did not express enhanced bactericidal activities. The collective results indicate that antiorthostatic suspension can stimulate profiles of macrophage activation which correlate with increased resistance to infection by certain classes of pathogenic bacteria.

Hypergravity-induced immunomodulation in a rodent model: hematological and lymphocyte function analyses

“…When mice were suspended for 7 days before inoculation, clearance was still enhanced but not to the extent seen for days 2 and 4 (30,32). Furthermore, EL-4stimulated splenocytes from animals exposed to 4 days of suspension had significantly higher levels of IL-1 activity compared with vivarium controls in both naive and Listeria inoculated mice (30). In contrast, Gould et al (13) found that mice inoculated with a normally resisted dose of encephalomyocarditis virus on day 0 began to die within 4 days of suspension.…”

“…However, when mice were inoculated 2 or 4 days into a 7-to 9-day suspension, clearance was actually enhanced. When mice were suspended for 7 days before inoculation, clearance was still enhanced but not to the extent seen for days 2 and 4 (30,32). Furthermore, EL-4stimulated splenocytes from animals exposed to 4 days of suspension had significantly higher levels of IL-1 activity compared with vivarium controls in both naive and Listeria inoculated mice (30).…”

Effect of Long-Term Antiorthostatic Suspension in a Murine Model of Acute Lung Injury

“…Miller et al [19] suggested that the profiles of macrophage activation were increased after 4 days of AOS. However, they also suggested that these results could be highly dependent on several factors, such as the duration of AOS and ability of adaptation in each individual [19]. The duration of AOS in our study was 4 weeks, which is still longer period than previous studies.…”

“…In fact, there was no significant difference comparing MPO of lung homogenate between restraint and AOS group. Miller et al [19] suggested that AOS for 4 days had protective effect for Listeria monocytogenes infection through activation of macrophages. On the other hand, Belay et al [29] suggested that mice exposed to AOS for 2 days had less resistance and higher fatality for infection of Klebsiella pneumoniae .…”

Spaceflight: Immune Effects and Nutritional Countermeasure

“…Like all the objects, microbes are also in free-floating state increasing the potential for inoculation by inhalation increasing the regional susceptibility of respiratory tract. Altered metabolism and virulence reported in in vivo models of simulatory microgravity [31][32][33][34][35]. Increased morbidity and slower rate of wound healing in S. aureus sepsis reported in experimental animals exposed to test environment.…”