In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 83, No. 6 ( 2008-06-01), p. 1423-1430
Abstract:
Neutrophils play an important role in immune complex (IC)-mediated diseases, but the mechanisms underlying their recruitment to sites of IC deposition remain largely undefined. Furthermore, neutrophils encounter cytokines that prime their effector functions, yet the physiological relevance of priming to neutrophil functions is unclear. Using intravital microscopy, we demonstrate that TNF treatment of neutrophils ex vivo significantly increased their adhesion in a model of intravascular ICs deposited in the cremaster muscle. Notably, TNF priming had no effect on neutrophil adhesion in the absence of ICs. Analyses of relevant knockout mice and neutrophil reconstitution revealed a critical role for FcγRs and the CD18 integrin Mac-1 in IC-mediated neutrophil adhesion. Furthermore, ICAM-1, a major Mac-1 ligand constitutively expressed on unactivated endothelium, significantly contributed to this process. These data suggest that TNF priming promotes FcγR interaction with intravascular ICs, leading to the binding of Mac-1 to ICAM-1 and subsequent neutrophil arrest.
Type of Medium:
Online Resource
ISSN:
0741-5400
,
1938-3673
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2008
detail.hit.zdb_id:
2026833-6
SSG:
12
