RELATIONSHIP OF HISTAMINE-RELEASING FACTORS TO THE HUMAN INTERCRINE CHEMOKINE GROUP OF CYTOKINE-LIKE MOLECULES

Histamine Releasing Factors have been characterized as a product of human mononuclear cells and platelets. MCAF/MCP-1, a monocyte-derived product is the most potent one described which acts rapidly (within 1 minute) upon basophils of over 90% of subjects tested. RANTES, a product of a subpopulation of CD4(+) lymphocytes acts similarly but is about half as potent. CTAP III/NAP-2, by contrast, is a platelet derived HRF of low potency. It is, however, a plentiful protein and NAP-2, is derived from CTAP III by cleavage with elastase. All are members of the intercrine/chemokine group of cytokine-like molecules many of which are chemotactic factors and/or activate other cells. Interleukin 8 (NAP-1), another chemokine inhibits histamine release induced by all known forms of HRF. Interleukin 3 is a primer of basophils but at high concentrations can itself induce histamine release from a subpopulation (mainly atopic) of subjects. These proteins are thought to be important mediators of protracted inflammation and histamine release seen in allergic late phase reactions and, perhaps in specific disorders such as chronic urticaria, atopic dermatitis, scleroderma, and rheumatoid arthritis.