Switch of histamine receptor expression from H2 to H1 during differentiation of monocytes into macrophages

It is known that histamine suppresses gene expression and synthesis of tumo r necrosis factor alpha (TNF-alpha) induced by lipopolysaccharide (LPS) in human peripheral blood mononuclear monocytes (HPM) or alveolar macrophages via histamine H2 receptors. We investigated the effect of histamine and dif ferentiation in macrophages an the expression and secretion of TNF-alpha TN F-alpha-converting enzyme (TACE), and histamine H1 and H2 receptors by use of a leukemia cell line, U937, and HPM. Differentiation of U937 and HPM cel ls with 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced the H1 receptor expression and rather suppressed the H2 receptor, resulting in up-regulati on of the histamine-induced expression and secretion of TNF-alpha, modulate d via TACE. Therefore, histamine failed to inhibit up-regulated expression of TNF-alpha induced by LPS in macrophages. The switch from H2 to H1 recept ors during differentiation in the monocyte/macrophage lineage could partici pate in the pathogenic processes of atherosclerosis and inflammatory reacti ons in the arterial wall. (C) 2000 Federation of European Biochemical Socie ties.