Gc-globulin (vitamin D-binding protein) enhances the neutrophil chemotactic activity of C5a and C5a des Arg

J Clin Invest. 1988 Jul;82(1):364-9. doi: 10.1172/JCI113596.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anaphylatoxins
  • Chemotaxis, Leukocyte / drug effects*
  • Complement C5 / analogs & derivatives*
  • Complement C5 / physiology*
  • Complement C5a
  • Complement C5a, des-Arginine
  • Dose-Response Relationship, Immunologic
  • Drug Synergism
  • Humans
  • Neutrophils / drug effects
  • Neutrophils / physiology*
  • Vitamin D-Binding Protein / blood
  • Vitamin D-Binding Protein / physiology*


  • Anaphylatoxins
  • Complement C5
  • Complement C5a, des-Arginine
  • Vitamin D-Binding Protein
  • Complement C5a