title: Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties.
abstract: 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.
authors.affiliation: Laboratory of Medical Biochemistry, Rockefeller University, New York.
authors.forename: S D
authors.initials: SD
authors.lastname: Wolpe
authors.forename: G
authors.initials: G
authors.lastname: Davatelis
authors.forename: B
authors.initials: B
authors.lastname: Sherry
authors.forename: B
authors.initials: B
authors.lastname: Beutler
authors.forename: D G
authors.initials: DG
authors.lastname: Hesse
authors.forename: H T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: C F
authors.initials: CF
authors.lastname: Nathan
authors.forename: S F
authors.initials: SF
authors.lastname: Lowry
authors.forename: A
authors.initials: A
authors.lastname: Cerami
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001688:Biological Products / Q000302:isolation & purification / Q000502:physiology*; D002352:Carrier Proteins / Q000302:isolation & purification / Q000502:physiology*; D002630:Chemotactic Factors / Q000302:isolation & purification / Q000502:physiology*; D005260:Female; D006493:Heparin / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D016209:Interleukin-8; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D015846:Monokines
chemical_list: D001688:Biological Products; D002352:Carrier Proteins; D002630:Chemotactic Factors; D016209:Interleukin-8; D015846:Monokines; D006493:Heparin; D006861:Hydrogen Peroxide