Macrophage inflammatory protein-1α activates basophils 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-1α on histamine secretion from basophils and mast cells. Leukocytes from allergic and normal subjects were studied. MIP-1α 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-1α. Histamine release by MIP-1α was rapid, and almost complete within the first 3 min. MIP-1α-induced degranulation was a calcium-dependent noncytotoxic process. MIP-1α showed chemotactic activity for purified basophils that was comparable to MCAF. Both MIP-1α and MCAF at 10^-7 M concentration elicited a chemotactic response that was 40% of the maximal response to C5a (1 μg/ml). Murine MIP-1α induced histamine release from mouse peritoneal mast cells in a dose-dependent manner. Thus, we have established that MIP-1α is a novel activator of basophils and mast cells.