Macrophage Inflammatory Protein-1 is a factor produced by macrophages that causes local inflammatory responses, and induces superoxide production by neutrophils . Two peptides are responsible for this activity, termed MIP-1-alpha, and MIP-1-beta. The two MIP proteins are the major factors produced by macrophages following their stimulation with bacterial endotoxins. Both proteins are involved in the cell activation of human granulocytes (neutrophils, eosinophils, and basophils) and appear to be involved in acute neutrophilic inflammation. Both forms of MIP-1 stimulate the production of reactive oxygen species in neutrophils and the release of lysosomal enzymes. They also induce the synthesis of other pro-inflammatory cytokines such as IL-1, IL-6 and TNF in fibroblasts and macrophages. MIP-1-alpha is a potent agonist of basophils, inducing a rapid change of cytosolic free calcium, the release of histamine and sulfido-leukotrienes, and chemotaxis. Murine MIP-1- alpha is the primary stimulator of TNF secretion by macrophages, whereas MIP- 1-beta antagonizes the inductive effects of MIP-1-alpha. In human monocytes, the production of MIP-1-beta can be induced by bacterial lipopolysaccharides and IL-7. The biological activities of MIP-1-alpha and MIP-1-beta are mediated by CCR5, a receptor that binds both factors. A second species of receptors for these two factors also appears to bind MCAF.