THE MECHANISM OF HISTAMINE PRODUCTION IN ALLERGIC INFLAMMATION

In the air pouch-type allergic inflammation model in mrs, histamine pr oduced in the late phase plays a role in downregulation of leukocyte i nfiltration into the pouch fluid. In the pouch fluid, we found two kin ds of histamine production-increasing factor (HPIF); HPIF-1, which ind uces histamine production in bone marrow cells, and HPIF-2, which enha nces tile activity of HPIF-1. Isoelectric point and molecular weight o f HPIF-1 and HPIF-2 were estimated to be pi 4-5 and 25-40 kD, and pi 7 -8 and about 100 kD, respectively. The histamine-producing ability of bone marrow cells increased after the antigen challenge, but that of p eripheral leukocytes decreased markedly 8 h after the antigen challeng e. Pharmacological analysis indicated that HPIF-1 induces histamine pr oduction through activation of protein kinase C and tyrosine kinase. D ifferentiation of bone marrow cells to histamine-producing cells by HP IF-1 was also indicated From these observations, the histamine product ion in the late phase of allergic inflammation is suggested to be regu lated by the production of HPIF-1, proliferation/differentiation of hi stamine-producing cells, and infiltration of histamine-producing cells in blood circulation into the inflammatory site.