This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Norman, M. U. Articles by Hickey, M. J. Search for Related Content PubMed PubMed Citation Articles by Norman, M. U. Articles by Hickey, M. J.

(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.

This article has been cited by other articles:

				J. Apostolopoulos, M. J. Hickey, L. Sharma, P. Davenport, L. Moussa, W. G. James, J. L. Gregory, A. R. Kitching, M. Li, and P. G. Tipping The cytoplasmic domain of tissue factor in macrophages augments cutaneous delayed-type hypersensitivity J. Leukoc. Biol., April 1, 2008; 83(4): 902 - 911. [Abstract] [Full Text] [PDF]

				R. Sumagin and I. H. Sarelius A role for ICAM-1 in maintenance of leukocyte-endothelial cell rolling interactions in inflamed arterioles Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2786 - H2798. [Abstract] [Full Text] [PDF]

				R. T. Sasmono, A. Ehrnsperger, S. L. Cronau, T. Ravasi, R. Kandane, M. J. Hickey, A. D. Cook, S. R. Himes, J. A. Hamilton, and D. A. Hume Mouse neutrophilic granulocytes express mRNA encoding the macrophage colony-stimulating factor receptor (CSF-1R) as well as many other macrophage-specific transcripts and can transdifferentiate into macrophages in vitro in response to CSF-1 J. Leukoc. Biol., July 1, 2007; 82(1): 111 - 123. [Abstract] [Full Text] [PDF]

				H. Orito, M. Fujimoto, N. Ishiura, K. Yanaba, T. Matsushita, M. Hasegawa, F. Ogawa, K. Takehara, and S. Sato Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 cooperatively contribute to the cutaneous Arthus reaction J. Leukoc. Biol., May 1, 2007; 81(5): 1197 - 1204. [Abstract] [Full Text] [PDF]

				F. W. Luscinskas and T. Mayadas Fc{gamma}Rs join in the cascade Blood, May 1, 2007; 109(9): 3615 - 3616. [Full Text] [PDF]

				K. J. Lister and M. J. Hickey Immune complexes alter cerebral microvessel permeability: roles of complement and leukocyte adhesion Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H694 - H704. [Abstract] [Full Text] [PDF]

				M. P. Kuligowski, A. R. Kitching, and M. J. Hickey Leukocyte Recruitment to the Inflamed Glomerulus: A Critical Role for Platelet-Derived P-Selectin in the Absence of Rolling. J. Immunol., June 1, 2006; 176(11): 6991 - 6999. [Abstract] [Full Text] [PDF]

				M. Aurrand-Lions, C. Lamagna, J. P. Dangerfield, S. Wang, P. Herrera, S. Nourshargh, and B. A. Imhof Junctional Adhesion Molecule-C Regulates the Early Influx of Leukocytes into Tissues during Inflammation J. Immunol., May 15, 2005; 174(10): 6406 - 6415. [Abstract] [Full Text] [PDF]

				T. Stokol, P. O'Donnell, L. Xiao, S. Knight, G. Stavrakis, M. Botto, U. H. von Andrian, and T. N. Mayadas C1q Governs Deposition of Circulating Immune Complexes and Leukocyte Fc{gamma} Receptors Mediate Subsequent Neutrophil Recruitment J. Exp. Med., October 4, 2004; 200(7): 835 - 846. [Abstract] [Full Text] [PDF]