A role for Mac-1 (CDIIb/CD18) in immune complex-stimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fcgamma receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis

J Exp Med. 1997 Dec 1;186(11):1853-63. doi: 10.1084/jem.186.11.1853.


Mac-1 (alphambeta2), a leukocyte adhesion receptor, has been shown in vitro to functionally interact with Fcgamma receptors to facilitate immune complex (IC)-stimulated polymorphonuclear neutrophil (PMN) functions. To investigate the relevance of Mac-1-FcgammaR interactions in IC-mediated injury in vivo, we induced a model of Fc-dependent anti-glomerular basement membrane (GBM) nephritis in wild-type and Mac-1-deficient mice by the intravenous injection of anti-GBM antibody. The initial glomerular PMN accumulation was equivalent in Mac-1 null and wild-type mice, but thereafter increased in wild-type and decreased in mutant mice. The absence of Mac-1 interactions with obvious ligands, intercellular adhesion molecule 1 (ICAM-1), and C3 complement, is not responsible for the decrease in neutrophil accumulation in Mac-1- deficient mice since glomerular PMN accumulation in mice deficient in these ligands was comparable to those in wild-type mice. In vitro studies showed that spreading of Mac-1-null PMNs to IC-coated dishes was equivalent to that of wild-type PMNs at 5-12 min but was markedly reduced thereafter, and was associated with an inability of mutant neutrophils to redistribute filamentous actin. This suggests that in vivo, Mac-1 is not required for the initiation of Fc-mediated PMN recruitment but that Mac-1-FcgammaR interactions are required for filamentous actin reorganization leading to sustained PMN adhesion, and this represents the first demonstration of the relevance of Mac-1-FcgammaR interactions in vivo. PMN-dependent proteinuria, maximal in wild-type mice at 8 h, was absent in Mac-1 mutant mice at all time points. Complement C3-deficient mice also had significantly decreased proteinuria compared to wild-type mice. Since Mac-1 on PMNs is the principal ligand for ic3b, an absence of Mac-1 interaction with C3 probably contributed to the abrogation of proteinuria in Mac-1-null mice.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Acute Disease
  • Animals
  • Anti-Glomerular Basement Membrane Disease / complications
  • Anti-Glomerular Basement Membrane Disease / immunology*
  • Anti-Glomerular Basement Membrane Disease / pathology
  • Basement Membrane / immunology
  • Capillary Permeability
  • Cell Adhesion
  • Complement C3b / deficiency
  • Complement C3b / genetics
  • Complement C3b / metabolism
  • Complement System Proteins / immunology*
  • Endothelium, Vascular / pathology
  • Female
  • Immune Complex Diseases / complications
  • Immune Complex Diseases / immunology*
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / physiology
  • Isoantibodies / immunology
  • Isoantibodies / toxicity
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Leukotriene B4 / biosynthesis
  • Macrophage-1 Antigen / genetics
  • Macrophage-1 Antigen / metabolism
  • Macrophage-1 Antigen / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Immunological
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Proteinuria / etiology*
  • Proteinuria / pathology
  • Receptors, IgG / physiology*


  • Actins
  • Isoantibodies
  • Macrophage-1 Antigen
  • Receptors, IgG
  • Intercellular Adhesion Molecule-1
  • Leukotriene B4
  • Complement C3b
  • Complement System Proteins