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Complement C5a Receptor is the Key Initiator of Neutrophil Adhesion Igniting
Immune Complex-induced Arthritis
#MMPMID28529998
Miyabe Y
; Miyabe C
; Murooka TT
; Kim EY
; Newton GA
; Kim ND
; Haribabu B
; Luscinskas FW
; Mempel TR
; Luster AD
Sci Immunol
2017[Jan]; 2
(7
): ? PMID28529998
show ga
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 initiate and propagate 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 ?2 integrin-dependent
neutrophil arrest, facilitating neutrophil spreading and transition to crawling,
and subsequent leukotriene B(4) 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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