Serotonin-induced production of a monocyte chemotactic factor by human peripheral blood leukocytes

Serotonin and histamine are released during the early phase of inflammatory reactions. To determine if these vasoactive amines might play a role in the cell-mediated phase of inflammation, studies were undertaken to assess their influence on some immunologic functions of human peripheral blood leukocytes (PBL). PBL were cultured with serotonin or histamine, and assayed for a proliferative response and their cell-free supernatants were assayed for the presence of a mediator with chemotactic activity for monocytes. Neither serotonin nor histamine were directly chemotactic for monocytes. When serotonin was cultured with PBL factors chemotactic for monocytes as well as polymorphonuclear leukocytes were produced in the absence of a proliferative response. Production of the factor chemotactic for monocytes was specifically blocked by methysergide, a serotonin antagonist and nonspecifically blocked by cycloheximide which interferes with leukocyte protein synthesis. Some dearboxylated precursors of serotonin also induced the monocyte chemotactic factor. This serotonin-induced chemotactic factor was demonstrated to be a product of mononuclear cells, and the majority of chemotactic activity was physiochemically similar to the previously characterized lymphocyte-derived chemotactic factor, suggesting that this factor is a lymphocyte product. In contrast to serotonin, histamine did not stimulate the production of monocyte chemotactic factor, nor did it induce proliferation. However, when 10(-5) M histamine was added to a substimulatory concentration of serotonin (10(-5) M), chemotactic activity comparable to or greater than the peak activity of serotonin alone was measured. This synergistic effect between serotonin and histamine suggests that the combination of these two amines may contribute to the induction of monocyte exudation in inflammatory reactions.