Platelet leukocyte interactions. II. In-vivo correction of Chediak-Higashi leukocyte function with serotonin or normal platelets.

Abstract

The formed elements of the peripheral blood often are characterized according to their separate primary functions in homeostasis. While these elements perform independently of each other, there is increasing evidence documenting an essential interaction between these formed elements. Some of these interactions, for example, have been shown to involve lymphocyte subtypes or lymphocytes and macrophages in cellular and humoral immunity1, and more recently, the relationship of neutrophilic metabolic activation to the platelet release reaction has been demonstrated2–7. We recently have presented evidence for the reversed interaction between neutrophils and platelets where a component of platelet dense bodies affects neutrophil function8. In these studies, platelet-leukocyte interactions were evaluated in-vitro, using the beige mouse, an animal model of the Chediak-Higashi (CH) syndrome, where both platelet and leukocyte function are defective. These studies demonstrated that normal platelets, or serotonin, a constituent of normal platelet-dense bodies which is absent in CH platelets, corrects the abnormal microbicidal activity of CH peripheral blood leukocytes. The present study further tests the hypothesis that platelet serotonin acts as an effector of PMN function be evaluating the effect of intravenous administration of normal platelets or of serotonin on CH leukocyte microbicidal activity, relating our findings to resulting platelet and plasma serotonin levels. The fate of the injected serotonin also was determined, and it was demonstrated that large amounts of the metabolite 5 hydroxyindole acetic acid (5-HIAA) are formed. This substance, however, has no effect on leukocyte function. These studies confirmed our initial in-vitro observations and showed that CH leukocyte function may be corrected in-vivo by normal platelets or serotonin but not by serotonin breakdown products.