Mechanism of histamine release by formyl methionine-containing peptides.
Small, acylated, methionine-containing peptides release histamine from human basophils. The characteristics of this reaction were compared to that of C5a- and IgE-induced release. fMet peptide-induced release requires Ca++ and is inhibited by EDTA in a manner similar to IgE- and C5a-mediated reactions. The fMet-Phe-Met-initiated reaction is complete within 2 min at temperatures of 25, 30, and 37 degrees C; but does not occur at 0 degrees C. There was a large variation in the capacity of leukocytes from different donors to release histamine with fMet peptides. However, there was no correlation in the capacity of leukocytes to release histamine with fMet-Phe-Met and their release with C5a or anti-IgE. The release by fMet-Phe-Met (but not by C5a or anti-IgE) was reversibly inhibited by a nonreleasing tripeptide. Leukocytes could be desensitized to the action of active fMet-peptide by preincubation with the peptide in the absence of cations. After washing, these cells released normally with C5a or anti-IgE. Conversely, cells desensitized to the action of C5a- or IgE-mediated reactions released normally with fMet peptides. There was cross-desensitization between different active peptides, and inactive peptides could not desensitize the leukocytes. Pharmacologic agents had similar effects on C5a and fMet peptide-induced release (e.g., lack of enhancement with deuterium oxide; enhancement with cytochalasin B; and inhibition with aminophylline and dibutyryl cyclic AMP). Therefore, histamine release with fMet peptides is initiated by their binding to and activation of a specific receptor on the basophil; the reaction beyond that point is similar to the C5a-mediated reaction.
D003182:Complement C5 / Q000378:metabolism; D003571:Cytochalasin B / Q000494:pharmacology; D003903:Deuterium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D008715:Methionine / Q000031:analogs & derivatives*; D009239:N-Formylmethionine / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D013696:Temperature; D013997:Time Factors
D003182:Complement C5; D010455:Peptides; D007073:Immunoglobulin E; D003571:Cytochalasin B; D009239:N-Formylmethionine; D008715:Methionine; D003903:Deuterium