Macrophage Inflammatory Protein-lc Activates Basophlh and Mast Cells

Macrophage inflammatory protein-1 (MIP) is a recently cloned cytokine that causes neutrophilic infiltration and induces an inflammatory response. We studied the effect of MIP-lo~ on histamine secretion from basophils and mast cells. Leukocytes from allergic and normal subjects were studied. MIP-loe caused dose-dependent release of histamine from basophils of 14 of 20 allergic donors at concentrations of 10-9-10 -7 M, and the mean release was 13.50 + 2.9% at the highest concentration. In the same experiments, the mean histamine release by anti-immunoglobulin E and monocyte chemotactic and activating factor (MCAF) (10 -7 M) was 32 + 7% and 31 _+ 3%, respectively. The cells from only 2 of 10 normal subjects released histamine in response to MIP-loe. Histamine release by MIP-lo~ was rapid, and almost complete within the first 3 rain. MIP-lce-induced degranulation was a calcium-dependent noncytotoxic process. MIP-lo~ showed chemotactic activity for purified basophils that was comparable to MCAF. Both MIP-lo~ and MCAF at 10-7 M concentration elicited a chemotactic response that was 40% of the maximal response to CSa (1/zg/ml). Murine MIP-lo~ induced histamine release from mouse peritoneal mast cells in a dose-dependent manner. Thus, we have established that MIP-lo~ is a novel activator of basophils and mast cells.