Modulation of the inflammatory response by products released from human polymorphonuclear leukocytes during phagocytosis

Abstract

During phagocytosis of latex particles human polymorphonuclear leukocytes (PMNs) release a product that generates chemotactic activity from fresh human serum. Release of this product is maximal at 20–30 min of phagocytosis. It is present in resting PMNs, may be recovered from granule fractions, and functions at physiologic pH. Gel-filtration chromatography of the activated serum indicates that C5a accounts for most of the chemotactic activity generated. Studies utilizing preparations of C5, EDTA, magnesium-EGTA, CS-deficient serum, and serum heated for 20 min at 50°C demonstrate that generation of C5a results from activation of the complement system as well as from direct cleavage of C5. Activation of the complement system by this PMN-derived serum activator appears to proceed through both the alternate and classical pathways. In addition to this serum activator, an inactivator of C5a chemotactic activity is also released by the PMNs under certain conditions of phagocytosis. These studies suggest that phagocytizing PMNs have secretory functions that contribute to the localization and amplification of inflammatory responses.