title: Gc-globulin (vitamin D-binding protein) enhances the neutrophil chemotactic activity of C5a and C5a des Arg.
abstract: Several serum proteins have been shown to be important in modulating leukocyte chemotaxis and inflammation. We investigated the possibility that the multifunctional serum protein Gc-globulin (vitamin D-binding protein) may also enhance the neutrophil chemotactic activity of complement-derived peptides. Purified Gc-globulin by itself did not induce chemotaxis of human neutrophils. However, as little as 0.01 nM Gc-globulin greatly enhanced the neutrophil chemotactic activity of C5a and its derivative, C5a des Arg over a wide concentration range. The effect was most pronounced at nonchemotactic doses of C5a (0.01 nM) and C5a des Arg (1 nM). Gc-globulin was unable to augment the neutrophil chemotactic activity of FMLP and leukotriene B4. This enhancing activity was not due to a nonspecific effect of anionic proteins since other purified serum proteins, of similar size and charge as Gc-globulin (alpha 1 acid glycoprotein, alpha 2 HS glycoprotein, alpha 2 histidine-rich glycoprotein), could not increase the chemotactic activity of C5a des Arg. Serum depleted of Gc-globulin by immunoaffinity chromatography totally lacked chemotactic enhancing activity for C5a des Arg. Gc-globulin-depleted serum activated with zymosan also had significantly less chemotactic activity than control- (sham-depleted) activated serum. Finally, radioiodinated C5a or C5a des Arg formed a 1:1 complex with purified Gc-globulin when analyzed by gel filtration chromatography. These results indicate that Gc-globulin is the major chemotactic enhancing factor in serum and may function as an up-regulator of the chemotactic activity of C5-derived peptides.
authors.affiliation: Department of Internal Medicine, St. Louis University School of Medicine, Missouri 63104.
authors.forename: R R
authors.initials: RR
authors.lastname: Kew
authors.forename: R O
authors.initials: RO
authors.lastname: Webster
mesh_terms: D000706:Anaphylatoxins; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003182:Complement C5 / Q000031:analogs & derivatives* / Q000502:physiology*; D015936:Complement C5a; D015937:Complement C5a, des-Arginine; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D014809:Vitamin D-Binding Protein / Q000097:blood / Q000502:physiology*
chemical_list: D000706:Anaphylatoxins; D003182:Complement C5; D015937:Complement C5a, des-Arginine; D014809:Vitamin D-Binding Protein; D015936:Complement C5a