Induction of local inflammation by recombinant human platelet factor 4 in the mouse.
Platelet factor 4 (PF-4) has been shown to be chemotactic for neutrophils and monocytes in vitro. To assess whether these observations have in vivo relevance, we tested the ability of recombinant human PF-4 (rPF-4) to induce acute and chronic dermal inflammation in the mouse. When injected as a single dose intradermally, rPF-4 induced an acute inflammatory response that peaked at 6 to 12 hr and which resolved by 36 hr. Injection of an equivalent amount of cytochrome c, buffer alone, or an amino-terminal PF-4 peptide failed to elicit a significant inflammatory response; however, the carboxy-terminal PF-4 peptide retained proinflammatory properties. The inflammatory infiltrate induced by a single injection of either rPF-4 or the 41 amino acid carboxy-terminal peptide was composed of neutrophils and smaller numbers of mononuclear cells. Repeated injection of rPF-4 resulted in nearly equal numbers of neutrophils and mononuclear cells. Moreover, marked dermal fibrosis developed after only 5 days of daily injection of rPF-4. Although relatively high concentrations of rPF-4 were required to elicit an inflammatory response, these concentrations may be locally attainable during platelet aggregation. Our findings thus support the hypothesis that PF-4 may contribute to the development of inflammatory responses at sites of platelet aggregation.
Sharpe
R J
RJ
Repligen Corporation, Cambridge, Massachusetts 02139.
Murphy
G F
GF
Whitaker
D
D
Galli
S J
SJ
Maione
T E
TE
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000473:pathology; D010978:Platelet Factor 4 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins; D012867:Skin / Q000473:pathology
D011994:Recombinant Proteins; D010978:Platelet Factor 4; D007213:Indomethacin