Hemorrhagic Shock-Induced Alterations in Circulating and Bronchoalveolar Macrophage Nitric Oxide Production

• Published in: The Journal of surgical research 1995-07, Vol.59 (1), p.146-152
• Main Authors: Naziri, Wahid, Pietsch, James D., Appel, Sarah H., Cheadle, William G., Bergamini, Thomas M., Polk, Hiram C.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Lipopolysaccharides - pharmacology; Lung - microbiology; Lung Injury; Macrophages - metabolism; Macrophages, Alveolar - metabolism; Male; Medical sciences; Miscellaneous; Nitric Oxide - biosynthesis; Rats; Rats, Sprague-Dawley; Resuscitation; Shock, Hemorrhagic - immunology; Shock, Hemorrhagic - metabolism; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1995.1146

Local and systemic host immune functions are markedly altered after trauma. Activated macrophages (Mφ) 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 Mφ 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 4.5 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 Mφ were then isolated and examined. A monolayer of adherent Mφ was examined for NO production in resting state and after in vitro LPS stimulation. (1) HEM resulted in significantly reduced alveolar Mφ yield at 12 and 24 hr. (2) HEM increased NO production by circulating Mφ at 24 hr ( P < 0.05), while alveolar Mφ 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 Mφ 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 Mφ and delayed and brief activation of circulating Mφ. Alveolar and circulating Mφ are unable to significantly increase NO production in response to LPS stimulation during the later phases of HEM. These factors may alter host immune response differentially to local and systemic bacterial challenges after hemorrhage.