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

Spontaneous and all-trans-retinoic acid (RA)-induced differentiation o f normal human monocytes and of leukemic THP-1 monocytes into macropha ges resulted in a progressive loss of adenosine 3',5'-cyclic monophosp hate 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, R A treatment increased the abundance of the 4.5-kb messenger RNA of the H(2)R gene fourfold, suggesting transcriptional control by a RA respo nse element. Scatchard plots of [H-3]tiotidine binding indicated the e xpression of H(2)R with similar affinity and binding capacity in THP-1 monocytes and macrophages, while the conversion of normal monocytes i nto macrophages decreased H(2)R density from 91.8 to 43.1 fmol/mg prot ein, with no change in affinity (K-d = 9.9 to 11.2 nM). In THP-1 macro phages, histamine inhibited 4 beta-phorbol 12-myristate 13-acetate (PM A)-induced H2O2 formation via the activation of H-2 receptors. Express ion of the H(2)R gene, histamine accumulation, and histidine decarboxy lase activity were also demonstrated in normal human monocytes/macroph ages and peripheral lymphocytes. Histamine and H(2)R may therefore aff ect, via intracrine, autocrine, and paracrine pathways, various immune and inflammatory responses of the lymphoid and myeloid progenitors an d lineages in the bone marrow and peripheral tissues.