Human lupus serum induces neutrophil-mediated organ damage in mice that is enabled by Mac-1 deficiency

Florencia Rosetti, Naotake Tsuboi, Kan Chen, Hiroshi Nishi, Thomas Ernandez, Sanjeev Sethi, Kevin Croce, George Stavrakis, Jorge Alcocer-Varela, Diana Gómez-Martin, Nico Van Rooijen, Vasileios C. Kyttaris, Andrew H. Lichtman, George C. Tsokos, Tanya N. Mayadas

研究成果: Article査読

44 被引用数 (Scopus)

抄録

Systemic lupus erythematosus (SLE) is a chronic, multiorgan inflammatory autoimmune disorder associated with high levels of circulating autoantibodies and immune complexes. We report that passive transfer of human SLE sera into mice expressing the uniquely human FcγRIIA and FcγRIIIB on neutrophils induces lupus nephritis and in some cases arthritis only when the mice additionally lack the CD18 integrin, Mac-1. The prevailing view is that Mac-1 on macrophages is responsible for immune complex clearance. However, disease permitted by the absence of Mac-1 is not related to enhanced renal immune complex deposition or in situ C1q/C3 complement activation and proceeds even in the absence of macrophages. Instead, disease is associated with increased FcγRIIA-induced neutrophil accumulation that is enabled by Mac-1 deficiency. Intravital microscopy in the cremasteric vasculature reveals that Mac-1 mitigates FcγRIIA-dependent neutrophil recruitment in response to deposited immune complexes. Our results provide direct evidence that human SLE immune complexes are pathogenic, demonstrate that neutrophils are primary mediators of end organ damage in a novel humanized lupus mouse model, and identify Mac-1 regulation of FcγRIIA-mediated neutrophil recruitment as a key step in development of target organ damage. Copyright

本文言語English
ページ(範囲)3714-3723
ページ数10
ジャーナルJournal of Immunology
189
7
DOI
出版ステータスPublished - 01-10-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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