HISTAMINE H-2 RECEPTORS AND HISTIDINE-DECARBOXYLASE IN NORMAL AND LEUKEMIC HUMAN MONOCYTES AND MACROPHAGES

Spontaneous and all-trans-retinoic acid (RA)-induced differentiation of normal human monocytes and of leukemic THP-1 monocytes into macrophages resulted in a progressive loss of adenosine 3',5'-cyclic monophosphate production induced by histamine via typical H-2 receptors (H(2)R). In THP-1 cells and in HL-60 human acute myelocytic leukemia cells, RA treatment increased the abundance of the 4.5-kb messenger RNA of the H(2)R gene fourfold, suggesting transcriptional control by a RA response element. Scatchard plots of [H-3]tiotidine binding indicated the expression of H(2)R with similar affinity and binding capacity in THP-1 monocytes and macrophages, while the conversion of normal monocytes into macrophages decreased H(2)R density from 91.8 to 43.1 fmol/mg protein, with no change in affinity (K-d = 9.9 to 11.2 nM). In THP-1 macrophages, histamine inhibited 4 beta-phorbol 12-myristate 13-acetate (PMA)-induced H2O2 formation via the activation of H-2 receptors. Expression of the H(2)R gene, histamine accumulation, and histidine decarboxylase activity were also demonstrated in normal human monocytes/macrophages and peripheral lymphocytes. Histamine and H(2)R may therefore affect, via intracrine, autocrine, and paracrine pathways, various immune and inflammatory responses of the lymphoid and myeloid progenitors and lineages in the bone marrow and peripheral tissues.