Neutrophils and mast cells: Characterization of cells responsive to neutrophil-derived histamine-releasing activity (HRA-N)

Abstract

Supernatants from human neutrophils (polymorphonuclear leukocytes) contain a factor capable of causing temperature and calcium-dependent histamine release from rat basophil leukemia (RBL) cells, termed neutrophil-derived, histamine-releasing activity (HRA-N). HRA-N caused dose-related histamine release from human basophils (5% to 22% net) and from isolated human cutaneous mast cells (3% to 28% net). Equivalent amounts of histamine were released from human basophils, RBL cells, and cultured mouse P cells exposed to HRA-N (16.3 ± 3.4%, 12.2 ± 1.2%, and 15.5 ± 2.5%, respectively: p was not significant). Intradermal injections of HRA-N also caused chlorpheniramine-inhibitable blueing in vivo in rat and guinea pig skin. In general, supernatants that were active on RBL cells also induced histamine release from human basophils, although the magnitude of response to individual HRA-N preparation varied among basophil donors. HRA-N is stable to boiling and filters at a molecular weight >1000 daltons. Boiling enhances HRA-N, suggesting the presence of a heat-labile inhibitor of HRA-N. These data suggest that HRA-N is a heat-stable factor that causes histamine release from human basophils and human cutaneous mast cells, that HRA-N is active across species lines both in vivo and in vitro, and that HRA-N acts maximally to induce histamine release under physiologic conditions.