No abstract

Histamine, selective histamine H1- and H2-receptor agonists, and chemical analogues of these compounds lacking activity at histamine receptors, were tested as inhibitors of phytohaemagglutinin-induced human lymphocyte proliferation and zymosan-induced release of lysosomal enzymes from human polymorphs. No correlation was found between their inhibitory potency in these systems and their relative activity at histamine H1- or H2-receptors.

Histamine has been shown to inhibit a variety of immune responses including the antigen-induced, IgE mediated, release of histamine from sensitized human leucocytes and from sensitized monkey and dog mast cells. The inhibitory action of histamine appears to be mediated by action at a histamine H2-receptor. In in vitro experiments the H2-receptor antagonist metiamide has been shown to block this histamine effect and it has been suggested that H2-receptor antagonists could intensify immediate hypersensitivity reactions in vivo. The effects of the H2-receptor antagonist metiamide and cimetidine have been studied in in vitro and in vivo models of anaphylaxis in the guinea-pig. The amount of extracellular histamine found after antigen challenge is greater when an H2-receptor antagonist is present during the incubation of mast cells with antigen. Bronchoconstriction induced by antigen in sensitized guinea-pig is exacerbated only by high doses of cimetidine. Possible explanations for the mechanism of action involved are discussed.

(1) Three types of experiments showed that histamine is formed during the reaction of antigen (D. pteronyssinus) with leucocytes of allergic human subjects: (a) total histamine of leucocytes (extracted + released) was increased; (b) histamine-forming capacity (HFC) of leucocytes was stimulated by antigen in vitro; (c) HFC of leucocytes was stimulated by injecting antigen in vivo. (2) Stimulation of HFC of leucocytes by antigen may provide a new and sensitive (though cumbersome) in vitro test of allergy.

It is commonly held that certain leukocyte sub-populations adhere selectively to histamine-serum albumin conjugates. A large number of soluble histamine, ethylamine and dimethylaminopropylamine conjugates were synthesised and labelled with fluorescein isothiocyanate (FITC). Although a number of conjugates bound to mononuclear cells and granulocytes our data showed this binding to be non-specific. The binding of histamine conjugates to leukocytes was not inhibited by preincubation of cells with free histamine at concentrations of up to 10^––1Mnor was it pH sensitive. In addition, conjugates of ethylamine and dimethylaminopropylamine showed a similar binding pattern to that of histamine conjugates. We suggest that the observed binding may be due to modifications to the net charge of the carrier protein molecule.