Complement C5a Receptor is the Key Initiator of Neutrophil Adhesion Igniting Immune Complex-induced Arthritis

Overview

Journal Sci Immunol

Specialty Allergy & Immunology

Date 2017 May 23

PMID 28529998

Citations 48

Authors

Yoshishige Miyabe

Chie Miyabe

Thomas T Murooka

Edward Y Kim

Gail A Newton

Nancy D Kim

Bodduluri Haribabu

Francis W Luscinskas

Thorsten R Mempel

Andrew D Luster

Affiliations

Soon will be listed here.

Abstract

The deposition of immune complexes (IC) in tissues induces a "type III hypersensitivity" that results in tissue damage and underlies the pathogenesis of many autoimmune diseases. The neutrophil is the first immune cell recruited into sites of IC deposition and plays a critical role in shaping the overall tissue response. However, the mechanism by which IC and neutrophil infiltration into tissue is not known. Here, using intravital multiphoton joint imaging of IC-induced arthritis in live mice, we found that the complement C5a receptor (C5aR) was the key initiator of neutrophil adhesion on joint endothelium. C5a presented on joint endothelium induced β2 integrin-dependent neutrophil arrest, facilitating neutrophil spreading and transition to crawling, and subsequent leukotriene B receptor (BLT1)-mediated extravasation of the first neutrophils. The chemokine receptor CCR1 promoted neutrophil crawling on the joint endothelium while CXCR2 amplified late neutrophil recruitment and survival once in the joint. Thus, imaging arthritis has defined a new paradigm for type III hypersensitivity where C5a directly initiates neutrophil adhesion on the joint endothelium igniting inflammation.

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