Human C5a and C5a des Arg exhibit chemotactic activity for fibroblasts.
C5a and C5a des Arg are chemotactic factors for inflammatory cells but it is not known whether these agents are chemoattractants for fibroblasts. Accordingly, C5a, purified from zymosan-activated human, and C5a des Arg, prepared by incubating C5a with immobilized porcine carboxypeptidase B, were studied for fibroblast chemotactic activity. We observed that both C5a and C5a des Arg stimulated human skin fibroblasts and fetal bovine ligament fibroblasts to migrate in a concentration-dependent fashion, and that the migratory responses were similar in magnitude to the responses achieved with optimal concentrations of two known fibroblast chemoattractants, platelet-derived growth factor and human fibrinopeptide B. The peak responses to C5a and C5a des Arg occurred at approximately 10(-9)M. With ligament fibroblasts, there was a greater response to C5a des Arg than to C5a, but with human fibroblasts there was no difference. Cochemotaxin, which enhances the chemotactic activity of C5a des Arg for neutrophils, had no effect on C5a des Arg fibroblast chemotactic activity but appeared to increase the fibroblast chemotactic activity of C5a. These results indicate that the effects of C5a and C5a des Arg in vivo may extend to the recruitment of mesenchymal cells. Moreover, the findings represent another example of an activity retained by C5a after removal of its carboxyl terminal arginine.
Senior
R M
RM
Department of Medicine, Jewish Hospital, St. Louis, MO 63110.
Griffin
G L
GL
Perez
H D
HD
Webster
R O
RO
D000906:Antibodies / Q000502:physiology; D002630:Chemotactic Factors / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects; D003182:Complement C5 / Q000031:analogs & derivatives* / Q000276:immunology / Q000502:physiology*; D015936:Complement C5a; D015937:Complement C5a, des-Arginine; D003169:Complement Inactivator Proteins / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D012697:Serine Endopeptidases; D015291:Transforming Growth Factors / Q000276:immunology
D000906:Antibodies; D002630:Chemotactic Factors; D003182:Complement C5; D015937:Complement C5a, des-Arginine; D003169:Complement Inactivator Proteins; D007074:Immunoglobulin G; C041833:complement C5a-inhibitors; D015291:Transforming Growth Factors; D015936:Complement C5a; D012697:Serine Endopeptidases