Hemorrhagic shock-induced alterations in circulating and bronchoalveolar macrophage nitric oxide production.
Local and systemic host immune functions are markedly altered after trauma. Activated macrophages (M phi) are the major effector cells of protective immunity, mediated in part by nitric oxide (NO). This study was undertaken to determine the effects of hemorrhage (HEM) on M phi cytotoxic function as measured by NO production. Male Sprague-Dawley 350- to 400-g rats were studied. Sham animals only had their carotid artery exposed and ligated. Hemorrhaged animals had carotid artery cannulation followed by HEM to SBP of 40 mmHg, sustained for 45 min, followed by resuscitation with shed blood and crystalloid. Recovered animals were sacrificed (n = 5 each) at 6, 12, 24, and 72 hr after HEM; blood and alveolar M phi were then isolated and examined. A monolayer of adherent M phi was examined for NO production in resting state and after in vitro LPS stimulation. (1) HEM resulted in significantly reduced alveolar M phi yield at 12 and 24 hr. (2) HEM increased NO production by circulating M phi at 24 hr (P < 0.05), while alveolar M phi had significantly increased NO production at all time points after HEM (P < 0.05). (3) LPS stimulation significantly increased NO production in both circulating and alveolar M phi in sham animals and 6 hr after HEM but not at any other times. We therefore conclude that HEM causes early and prolonged activation of NO production by alveolar M phi and delayed and brief activation of circulating M phi. Alveolar and circulating M phi are unable to significantly increase NO production in response to LPS stimulation during the later phases of HEM.(ABSTRACT TRUNCATED AT 250 WORDS)
Naziri
W
W
Department of Surgery, Price Institute of Surgical Research, University of Louisville, Kentucky 40292, USA.
Pietsch
J D
JD
Appel
S H
SH
Cheadle
W G
WG
Bergamini
T M
TM
Polk
H C
HC
D000818:Animals; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000382:microbiology; D055370:Lung Injury; D008264:Macrophages / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide