THE ROLE OF HISTAMINE IN PLATELET-AGGREGATION BY PHYSIOLOGICAL AND IMMUNOLOGICAL STIMULI

Background: Platelets participate in allergic and inflammatory process es beside their role in haemostasis and thrombosis. This paper reports the level, the uptake, the metabolism and the release of histamine in human platelets. The effects of exogenous histamine, as well as the r eceptor and signal transduction of these effects, are also described. Methods: Purified suspensions of platelets, prepared from healthy volu nteers and from atopic patients, were exposed in vitro to physiologica l and immunological stimuli. Platelet aggregation was measured by the increase in light transmission histamine content and release, as well as cytosolic free Ca(2+ )concentration, were measured fluorimetrically . Platelet histamine forming capacity, and the uptake of exogenous his tamine, were measured with a radioisotopic method. Results: Human plat elets contain 72.5 +/- 9.6 pmoles of histamine x 10(9) platelets, and their capacity to form histamine is 18.7 +/- 3.5 pmoles h(-1 )g(-1) pr otein, which is reduced by alpha-fluoromethylhistidine (10(-5 )M) a se lective inhibitor of the specific histidine decarboxylase. Human plate lets take up the preformed amine by a calcium and energy-dependent pro cess, and the uptake of histamine is reduced by mepyramine, an H(1 )re ceptor antagonist, and N,N-diethyl-2-[4-(phenylmethyl) phenoxyl] ethan amine (10(-6 )M), a blocker of intracellular histamine receptors. Hist amine is also metabolized by human platelets. The exposure of platelet s to thrombin (10-60 mU ml(-1)) produced a progressive aggregation, as sociated with histamine release. The same is observed in platelets iso lated from atopic patients exposed to anti-IgE antibodies. Exogenous h istamine dose-dependently potentiates the aggregation induced by physi ological and immunological stimuli. In resting platelets cytosolic cal cium level (207 +/- 4.2 nM/10(8) platelets) is increased by thrombin a s well as by anti-IgE; this effect is potentiated by 10(-5) M histamin e. Conclusions: The synergistic effect between histamine and other mon oamines on platelet aggregation may explain same aspects of allergic v asculitis in which platelet aggregation is present.