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(American Journal of Pathology. 2003;163:1491-1503.)
© 2003 American Society for Investigative Pathology

Overlapping Roles of Endothelial Selectins and Vascular Cell Adhesion Molecule-1 in Immune Complex-Induced Leukocyte Recruitment in the Cremasteric Microvasculature

M. Ursula Norman^*, Nicholas C. Van De Velde^*, Jennifer R. Timoshanko^*, Andrew Issekutz and Michael J. Hickey^*

From the Centre for Inflammatory Diseases,^* Monash University, Victoria, Australia; and the Departments of Pediatrics, Microbiology-Immunology, and Pathology, Dalhousie University, Halifax, Nova Scotia, Canada

Many adhesion molecule pathways have been invoked as mediating leukocyte recruitment during immune complex-induced inflammation. However the individual roles of these molecules have not been identified via direct visualization of an affected microvasculature. Therefore, to identify the specific adhesion molecules responsible for leukocyte rolling and adhesion in immune complex-dependent inflammation we used intravital microscopy to examine postcapillary venules in the mouse cremaster muscle. Wild-type mice underwent an intrascrotal reverse-passive Arthus model of immune complex-dependent inflammation and subsequently, leukocyte-endothelial cell interactions and P- and E-selectin expression were assessed in cremasteric postcapillary venules. At 4 hours, the reverse-passive Arthus response induced a significant reduction in leukocyte rolling velocity and significant increases in adhesion and emigration. P-selectin expression was increased above constitutive levels whereas E-selectin showed a transient induction of expression peaking between 2.5 to 4 hours and declining thereafter. While E-selectin was expressed, rolling could only be eliminated by combined blockade of P- and E-selectin. However, by 8 hours, all rolling was P-selectin-dependent. In contrast, inhibition of vascular cell adhesion molecule-1 had a minimal effect on leukocyte rolling, but significantly reduced both adhesion and emigration. These observations demonstrate that immune complex-mediated leukocyte recruitment in the cremaster muscle involves overlapping roles for the endothelial selectins and vascular cell adhesion molecule-1.

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