ISSN:
1420-908X
Keywords:
Key words: Adhesion - β2-integrins - CD18 - Leukocyte - TNF-α
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract: Objective: To examine the role of CD18 in tumor necrosis factor-α (TNF-α)-induced leukocyte adhesion and extravasation in vivo.¶Material: Male wild-type (WT) and mutated mice with hypomorphic expression of CD18.¶Methods: Intravital microscopy was used to quantitate leukocyte-endothelium interactions provoked by TNF-α (0.5 μg) in the cremaster muscle and dorsal skin microcirculation. Tissue recruitment of leukocytes was evaluated in whole-mounts of the cremaster muscle and in air pouches in the dorsal skin after TNF-α stimulation.¶Results: TNF-α markedly increased venular leukocyte adhesion and recruitment in the cremaster muscle and skin in WT. Notably, in CD18-targeted animals, leukocyte adhesion triggered by TNF-α challenge was significantly reduced by 58% and 72% in venules of the cremaster muscle and skin, respectively. Moreover, in CD18-mutants, tissue accumulation of polymorhonuclear leukocytes (PMNLs) provoked by TNF-α in the muscle and skin was decreased by 84% and 70%, respectively. Interestingly, the observed level of reduction in TNF-α-induced neutrophil adhesion and recruitment in CD18 gene-targeted animals corresponded well with the decrease in CD18 expression on neutrophils from these mice, i.e. the surface density of CD18 was reduced by 77% in mutants compared to WT. Differential analysis revealed that the extravascular leukocytes comprised more than 90% PMNLs, indicating that neutrophils were the main inflammatory cell responding to TNF-α activation. Notably, the expression of CD18 increased by more than two-fold on extravasated neutrophils compared to circulating neutrophils in the peripheral blood both in WT and mutant animals.¶Conclusions: These findings suggest that CD18 is a dominant mediator of firm neutrophil adhesion to venular endothelial cells in the muscle and skin stimulated by TNF-α in vivo. In addition, this decreased adhesion in CD18-mutants attenuates leukocyte extravasation in response to TNF-α activation. Thus, inhibition of CD18-function may provide an important strategy to inhibit leukocyte recruitment in cytokine-dependent diseases.¶
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s000110050627
Permalink
