Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Tang, T; Rosenkranz, A; Assmann, KJM; Goodman, MJ; GutierrezRamos, JC; Carroll, MC; Cotran, RS; Mayadas, TN.
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; 186(11): 1853-1863.
Doi: 10.1084/jem.186.11.1853
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- Co-Autor*innen der Med Uni Graz
- Rosenkranz Alexander
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- Abstract:
- 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.
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- 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 -
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- Mice, Inbred C57BL -
- Mice, Knockout -
- Models, Immunological -
- Neutrophils - immunology Neutrophils - metabolism
- Proteinuria - etiology Proteinuria - pathology
- Receptors, IgG - physiology