Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties

doi:10.1084/jem.167.2.570

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Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties

SD Wolpe, G Davatelis, B Sherry, B Beutler, DG Hesse, HT Nguyen, LL Moldawer, CF Nathan, SF Lowry and A Cerami
Laboratory of Medical Biochemistry, Rockefeller University, New York.

We report the identification and purification of a new inflammatory monokine synthesized by the macrophage tumor cell line RAW 264.7 in response to endotoxin. This monokine, which we term "macrophage inflammatory protein" (MIP), is a doublet with an apparent molecular mass of approximately 8,000 daltons on SDS-PAGE but forms aggregates of greater than 2 x 10(6) daltons as assessed by gel filtration. Partial NH2-terminal amino acid sequence data reveal no significant homology with any previously described protein. Although the monokine is anionic under physiological conditions, it is one of two major macrophage- secreted proteins that bind to heparin at high salt concentrations. At 100 ng/ml or greater, MIP is chemokinetic for human polymorphonuclear cells and triggers hydrogen peroxide production. Subcutaneous injection of 10 ng or greater of MIP into footpads of C3H/HeJ mice elicits an inflammatory response, characterized by neutrophil infiltration. These findings suggest that MIP is an endogenous mediator that may play a role in the host responses that occur during endotoxemia and other inflammatory events.
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