Intracellular heterogeneity in adhesiveness of endothelium affects early steps in leukocyte adhesion

• Published in: American Journal of Physiology: Cell Physiology Vol. 291; no. 1; pp. C130 - C137
• Main Authors: Mundhekar, Ameya N, Bullard, Daniel C, Kucik, Dennis F
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.07.2006
• Subjects: Adhesion; Animals; Bone Marrow Cells - physiology; Cell adhesion & migration; Cell Adhesion - physiology; Cell Adhesion Molecules - physiology; Cells, Cultured; Cellular biology; Cytoplasm - physiology; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Intercellular Junctions - physiology; Intracellular Fluid - physiology; Leukocytes; Leukocytes - cytology; Leukocytes - physiology; Mice; Neutrophils - physiology; P-Selectin - physiology; Vascular Cell Adhesion Molecule-1 - physiology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00261.2005

Departments of 1 Biomedical Engineering, 2 Genetics, and 3 Pathology, University of Alabama at Birmingham, and 4 Pathology and Laboratory Medicine Service, Birmingham Department of Veterans Affairs Medical Center, Birmingham, Alabama Submitted 3 June 2005 ; accepted in final form 30 January 2006 Endothelial cell junctions are thought to be preferential sites for transmigration. However, the factors that determine the site of transmigration are not well defined. Our data show that the preferential role of endothelial cell junctions is not limited to transmigration but extends to earlier steps of leukocyte recruitment, such as rolling and arrest. We used primary mouse neutrophils and mouse aortic endothelium in a flow chamber system to compare adhesive interactions near endothelial cell junctions to interactions over endothelial cell centers. We found differences in both rolling velocity and arrest frequency for neutrophils at endothelial cell junctions vs. more central areas of endothelial cells. Differences were governed by adhesion molecule interactions, not local topography. Interestingly, the role of particular adhesion molecules depended on their location on the endothelial cell surface. Although ICAM-1 stabilized and slowed rolling over central areas of the cell, it did not influence rolling velocity over endothelial cell junctions. P-selectin and VCAM-1 were more important for rolling near endothelial cell junctions than E-selectin. This demonstrates that adhesive properties of endothelial cell junctions influence early events in the adhesion cascade, which may help explain how leukocytes are localized to sites of eventual transmigration. endothelial cells; rolling; selectins; integrins Address for reprint requests and other correspondence: D. F. Kucik, Univ. of Alabama at Birmingham, Ctr. for Biophysical Sciences and Engineering, CBSE, Rm. 239, 1025 18th St. South, Birmingham, AL 35294 (e-mail: kucik{at}uab.edu )