ALVEOLAR MACROPHAGE RESPONSE TO REMOTE ORGAN INJURY

Intestinal reperfusion (IR)-induced pulmonary edema has been related t o endogenous pulmonary thromboxane A(2) (TxA(2)) release. This study e xamines the hypothesis that alveolar macrophages (aM phi s) activated during IR are an important cellular source of TxA(2) in this model. An esthetized Sprague Dawley rats underwent 120 min of intestinal ischemi a and 60 min of reperfusion (IR) or sham operation (Sham). aM phi s we re isolated by bronchoalveolar lavage and incubated in Krebs buffer fo r 30 min, after which the supernatant was analyzed for TxB(2) (metabol ite of TxA(2)) and prostaglandin E-2. Other parameters of aM phi activ ation measured included lysosomal enzyme release (beta-glucuronidase), superoxide (O-2(-)) release, and procoagulant activity, aM phi s from animals sustaining IR generated more than twice as much TxA(2) and pr ostaglandin E-2 as did those isolated from controls (p <.05). Other ev idence of aM phi activation included a nearly 100-fold increase in pro coagulant activity, a 7-fold increase in beta-glucuronidase release, a nd a 2.5-fold increase in O-2(-) release over that of controls (p <.05 ). These data suggest that TxA(2) is a major eicosanoid product of aM phi s during IR and that aM phi s may be an important cellular partici pant in IR-induced pulmonary microvascular injury, either directly by releasing O-2(-), lysosomal enzymes, and pro-coagulant factors, or ind irectly by generating TxA(2).