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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1063-1069.
Prepublished online as a Blood First Edition Paper on October 18, 2005; DOI 10.1182/blood-2005-08-3123.
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Submitted August 3, 2005
Accepted September 26, 2005
Differential roles for 2 integrins in experimental autoimmune bullous pemphigoid
Zhi Liu*, Minglang Zhao, Ning Li, Luis A Diaz, and Tanya N Mayadas
Department of Dermatology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
Department of Dermatology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
* Corresponding author; email: zhiliu{at}med.unc.edu.
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 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 2 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 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 h. However, more neutrophils accumulated in the skin of Mac-1 KO mice compared to WT mice at early time points (2-4 h), which was associated with an increase in their survival as determined by apoptosis markers. These data suggest that 2 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.

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