Vitamin D3 binding protein (group-specific component) is a precursor for the macrophage-activating signal factor from lysophosphatidylcholine-treated lymphocytes

Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8539-43. doi: 10.1073/pnas.88.19.8539.

Abstract

A brief (30 min) treatment of mouse peritoneal cells (mixture of nonadherent lymphocytes and adherent macrophages) with 1-20 micrograms of lysophosphatidylcholine (lyso-PC) per ml in serum-supplemented RPMI medium 1640, followed by a 3-hr cultivation of the adherent cells alone, results in a greatly enhanced Fc receptor-mediated phagocytic activity of macrophages. This rapid process of macrophage activation was found to require a serum factor, the vitamin D3 binding protein (the human protein is known as group-specific component; Gc). Efficient activation of macrophages was achieved by using medium containing purified human Gc protein. Analysis of intercellular signal transmission among nonadherent (B and T) cells revealed that lyso-PC-treated B cells modify Gc protein to yield a proactivating factor, which can be converted by T cells to the macrophage-activating factor. This rapid generation process of the macrophage-activating factor was also demonstrated by stepwise incubation of Gc protein with lyso-PC-treated B-cell ghosts and untreated T-cell ghosts, suggesting that Gc protein is modified by preexisting membranous enzymes to yield the macrophage-activating factor. Incubation of Gc protein with a mixture of beta-galactosidase and sialidase efficiently generated the macrophage-activating factor. Stepwise incubation of Gc protein with B- or T-cell ghosts and sialidase or beta-galactosidase revealed that Gc protein is modified by beta-galactosidase of B cells and sialidase of T cells to yield the macrophage-activating factor. Administration to mice of a minute amount (4-10 pg per mouse) of in vitro, enzymatically generated macrophage-activating factor resulted in a greatly enhanced (3- to 7-fold) ingestion activity of macrophages.

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Culture Media
  • Female
  • Glycoside Hydrolases / metabolism
  • In Vitro Techniques
  • Lymphocytes / physiology*
  • Lymphokines / physiology*
  • Lysophosphatidylcholines / pharmacology*
  • Macrophage Activation*
  • Mice
  • Mice, Inbred BALB C
  • Protein Precursors / metabolism
  • Vitamin D-Binding Protein / metabolism*

Substances

  • Culture Media
  • Lymphokines
  • Lysophosphatidylcholines
  • Protein Precursors
  • Vitamin D-Binding Protein
  • Glycoside Hydrolases