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Agonist leukadherin-1 Increases CD11b/CD18-dependent Adhesion via Membrane Tethers

Agonist leukadherin-1 Increases CD11b/CD18-dependent Adhesion via Membrane Tethers

Emrah Celik, Mohd Hafeez Faridi, Vinay Kumar, Shashank Deep, Vincent T Moy, Vineet Gupta

Biophys J. 2013 Dec 3;105(11):2517-27.

PMID: 24314082

Abstract:

Integrin CD11b/CD18 is a key adhesion receptor that mediates leukocyte migration and immune functions. Leukadherin-1 (LA1) is a small molecule agonist that enhances CD11b/CD18-dependent cell adhesion to its ligand ICAM-1. Here, we used single-molecule force spectroscopy to investigate the biophysical mechanism by which LA1-activated CD11b/CD18 mediates leukocyte adhesion. Between the two distinct populations of CD11b/CD18:ICAM-1 complex that participate in cell adhesion, the cytoskeleton(CSK)-anchored elastic elements and the membrane tethers, we found that LA1 enhanced binding of CD11b/CD18 on K562 cells to ICAM-1 via the formation of long membrane tethers, whereas Mn(2+) additionally increased ICAM-1 binding via CSK-anchored bonds. LA1 activated wild-type and LFA1(-/-) neutrophils also showed longer detachment distances and time from ICAM-1-coated atomic force microscopy tips, but significantly lower detachment force, as compared to the Mn(2+)-activated cells, confirming that LA1 primarily increased membrane-tether bonds to enhance CD11b/CD18:ICAM-1 binding, whereas Mn(2+) induced additional CSK-anchored bond formation. The results suggest that the two types of agonists differentially activate integrins and couple them to the cellular machinery, providing what we feel are new insights into signal mechanotransduction by such agents.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP344897956	Leukadherin-1		344897-95-6	Price

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