期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 284, 期 3, 页码 C705-C717出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00331.2002
关键词
protein kinases; adhesion molecules; antibodies; cellular activation
资金
- NIAID NIH HHS [AI-47294] Funding Source: Medline
- NIGMS NIH HHS [T32-GM-08799-01A1] Funding Source: Medline
Crosslinking of L-selectin on leukocytes signals phosphorylation of mitogen-activated protein kinases (MAPKs) leading to activation of CD18 function and enhanced transmigration on inflamed endothelium. We examined how alterations in the topography of L-selectin correlate with the dynamics of CD18 activation and phosphorylation of MAPK. Simultaneous ligation of humanized antibodies DREG55 and DREG200 provided a strategy for regulating the extent of cross-linking. Triggering of CD11b/CD18 upregulation and adhesion required clustering of L-selectin to microvillus-sized patches of similar to0.2 mum(2). Immunofluorescence revealed that L-selectin was colocalized with high-affinity CD18. Anti-L-selectin-coated protein A microspheres indicated that a single site of contact to a 5.5-mum bead, or multiple contacts to 0.94- or 0.3-mum beads, elicited maximum neutrophil activation. Adhesion signaled via L-selectin coincided with the kinetics of MAPK phosphorylation and was inhibited by blocking p38 or p42/44 activity. These data demonstrate the capacity of L-selectin to transduce signals effecting rapid (similar to1 s) neutrophil adhesion that is regulated by the size and frequency of receptor clustering.
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