Differential roles for beta2 integrins in experimental autoimmune bullous pemphigoid.
Bullous pemphigoid (BP) is an autoimmune disease associated with autoantibodies directed against the hemidesmosomal antigens anti-BP230 and anti-B180. Neonatal mice injected with rabbit anti-mouse BP180 (mBP10) IgG develop a BP-like disease. Complement, immune complexes, mast cells, and neutrophils play a key role in subepidermal blistering in this animal model. In this study we investigated the role of beta2 integrins in experimental BP. Wild-type (WT) mice pretreated with neutralizing antibody against CD11a (LFA-1), CD11b (Mac-1), CD11a plus CD11b, or CD18 alone failed to develop BP when injected with pathogenic anti-mBP180 IgG. This was associated with a significant reduction in neutrophil accumulation in neutralizing antibody-treated mice. Mac-1-deficient (Mac-1 knockout [KO]) mice were resistant to experimental BP despite normal complement deposition and mast cell and neutrophil degranulation. Neutrophil infiltration in Mac-1 KO mice was severely impaired at 24 hours. However, more neutrophils accumulated in the skin of Mac-1 KO mice compared with WT mice at early time points (2-4 hours), which was associated with an increase in their survival as determined by apoptosis markers. These data suggest that beta2 integrins play differential roles in experimental BP: LFA-1 is required for neutrophil recruitment, while Mac-1 mediates late neutrophil accumulation and apoptosis of infiltrating neutrophils.
Liu
Zhi
Z
Department of Dermatology, University of North Carolina, Chapel Hill, NC 27599, USA. zhiliu@med.unc.edu
Zhao
Minglang
M
Li
Ning
N
Diaz
Luis A
LA
Mayadas
Tanya N
TN
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000008:administration & dosage / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D004195:Disease Models, Animal; D022002:Hemidesmosomes / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018375:Neutrophil Activation / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010391:Pemphigoid, Bullous / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D001323:Autoantibodies; D018821:CD18 Antigens; D007074:Immunoglobulin G; D016177:Macrophage-1 Antigen; D003165:Complement System Proteins