HEMORRHAGIC SHOCK-INDUCED ALTERATIONS IN CIRCULATING AND BRONCHOALVEOLAR MACROPHAGE NITRIC-OXIDE PRODUCTION

Local and systemic host immune functions are markedly altered after tr auma. Activated macrophages (M phi) are the major effector cells of pr otective immunity, mediated in part by nitric oxide (NO). This study w as undertaken to determine the effects of hemorrhage (HEM) on M phi cy totoxic function as measured by NO production. Male Sprague-Dawley 350 - to 400-g rats were studied. Sham animals only had their carotid arte ry exposed and ligated. Hemorrhaged animals had carotid artery cannula tion followed by HEM to SEP of 40 mmHg, sustained for 45 min, followed by resuscitation with shed blood and crystalloid. Recovered animals w ere sacrificed (n = 5 each) at 6, 12, 24, and 72 hr after HEM; blood a nd alveolar M phi were then isolated and examined. A monolayer of adhe rent M phi was examined for NO production in resting state and after i n vitro LPS stimulation. (1) HEM resulted in significantly reduced alv eolar 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 signif icantly increased NO production at all time points after HEM (P < 0.05 ). (3) LPS stimulation significantly increased NO production in both c irculating and alveolar M phi in sham animals and 6 hr after HEM but n ot at any other times. We therefore conclude that HEM causes early and prolonged activation of NO production by alveolar M phi and delayed a nd brief activation of circulating M phi. Alveolar and circulating M p hi are unable to significantly increase NO production in response to L PS stimulation during the later phases of HEM. These factors may alter host immune response differentially to local and systemic bacterial c hallenges after hemorrhage. (C) 1995 Academic Press, Inc.