Enhanced phagocytosis, chemotaxis, and production of reactive oxygen intermediates by interstitial lung macrophages following acute endotoxemia.

Abstract

Endotoxemia is associated with enhanced release of a variety of cytotoxic and/or proinflammatory mediators from locally activated tissue macrophages. The lung is highly sensitive to damage induced by endotoxin, suggesting that pulmonary macrophages are activated by this bacterially derived product to release mediators that contribute to the pathogenesis of tissue injury. In the present studies, we used a rat model of acute endotoxemia induced by a single intravenous injection of animals with lipopolysaccharide (LPS) to determine the extent to which different lung macrophage subpopulations are activated. Alveolar macrophages (AM) and interstitial macrophages (IM) were isolated sequentially from the lung by lavage, followed by digestion with collagenase and selective adherence to tissue culture dishes. Both AM and IM were found to produce superoxide anion, as well as hydrogen peroxide in response to inflammatory stimuli. AM produced greater quantities of these reactive oxygen intermediates than did IM. Treatment of rats with LPS resulted in a significant increase in production of reactive oxygen intermediates by IM, but not by AM. Similarly, while AM from untreated rats phagocytized more opsonized sheep red blood cells than did IM, LPS treatment of rats significantly enhanced phagocytosis only in IM. In addition, this treatment caused a significant increase in chemotaxis of IM towards C5a. In contrast, although LPS treatment of rats had no effect on tumor necrosis factor-alpha release by AM, a significant reduction was observed in IM. Taken together, these data demonstrate that IM play a role in the inflammatory response of the lung to acute endotoxemia.