Role of Histamine in the Chemotactic Deactivation of Polymorphonuclear Leukocytes Following Incubation with Formylmethionyl Peptides

Abstract

To clarify the mechanism of chemotactic deactivation of polymorphonuclear neutrophils (PMN) following incubation with the synthetic dipeptide N-formylmethionyl phenylalanine (FMP), we tested the hypothesis that histamine, which is released from leukocytes during incubation with FMP, could explain this inhibition. Human PMN were incubated in the presence or absence of FMP (10^––7 to 10^––5M) and histamine measured fluorometrically in the supernatant. Washed PMN were then tested in Boyden chambers against FMP (10^––5M) and other chemoattractants. Incubation of leukocytes with FMP caused a nonpreferential PMN deactivation which was proportionally and kinetically related to FMP-induced histamine release. No histamine release or chemotactic deactivation was observed in the absence of Ca²⁺ and Mg²⁺. The inhibitory effect of the peptide was significantly prevented by an H₂ blocker or when using basophil-depleted PMN suspensions. Histaminase abolished the capacity of FMP-incubated leukocyte supernatants to decrease PMN chemotaxis. Preincubation of leukocytes with anti-IgE or a sensitizing allergen caused a significant PMN chemotactic deactivation. These results show that histamine, which is released during leukocyte incubation with FMP, contributes, at least in part, to the chemotactic deactivation of PMN.