1982 Activation of Basophil and Mast Cell Histamine

A frequent characteristic of immediate hypersensitivity reactions is systemic or localized tissue eosinophilia (1). This response is attributed to mast cell and basophil release of acidic tetrapeptides (2-4) and other products (5) preferentially chemotactic for eosinophils. Because of this association and eosinophil release of histaminase (6) and other mediators (7, 8) that may dampen allergic reactions, eosinophils are postulated to play an important role in the maintenance of local homeostasis during immediate hypersensitivity reactions (7, 8). Eosinophils and their products, however, are also recognized to have effector roles in various host defense mechanisms. In addition to their well-described participation in anti-parasitic events (8-10), eosinophil participation in bactericidal (11, 12) and tumoricidal (13) mechanisms is suggested, Major basic protein (MBP) I is a primary constituent of eosinophil granules. MBP, with a molecular weight of 9,300 in humans (14) and 11,000 in guinea pigs (15), is localized in the crystalline core of the eosinophil granule and comprises >50% of granule protein (16, 17). Release of MBP is implicated as a mechanism in eosinophilmediated killing of parasites (18, 19) and elevated levels of MBP have been observed in serum of individuals with eosinophilia (20) and at eosinophil-rich sites of inflammation (21). A characteristic feature of MBP is its high arginine content, ~11% for human MBP (14) and 13% for guinea pig MBP (15). It has previously been shown (22) that large molecular weight polymers of basic amino acids can induce histamine release from human leukocytes, with polymers of L-arginine being the most potent. Because of its significant arginine content, we postulated that human MBP might possess similar activity. In this report, we show that purified human MBP induces noncytolytic release of histamine from human basophils. We confirmed that the release is due to a direct effect of MBP on basophils using preparations of pure (92-96%) human basophils. Purified rat peritoneal mast cells display a similar response to MBP.