Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties.
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.
Wolpe
S D
SD
Laboratory of Medical Biochemistry, Rockefeller University, New York.
Davatelis
G
G
Sherry
B
B
Beutler
B
B
Hesse
D G
DG
Nguyen
H T
HT
Moldawer
L L
LL
Nathan
C F
CF
Lowry
S F
SF
Cerami
A
A
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
D001688:Biological Products; D002352:Carrier Proteins; D002630:Chemotactic Factors; D016209:Interleukin-8; D015846:Monokines; D006493:Heparin; D006861:Hydrogen Peroxide