Physiology in MedicineRoles of leukocyte/endothelial cell adhesion molecules in the pathogenesis of vasculitis
Section snippets
Leukocyte/endothelial cell adhesion molecules
Three major families of adhesion molecules have been described and include the selectins, integrins, and members of the immunoglobulin superfamily of adhesion receptors (Table 2)1, 2. These proteins mediate a wide variety of cell–cell interactions during normal immune and inflammatory responses, including leukocyte–leukocyte interactions, and leukocyte adhesion to endothelial cells, smooth muscle, extracellular matrix, and interstitial cells. A major function of these adhesion molecules is to
Adhesion molecule expression in human vasculitic diseases
There is now substantial experimental evidence that shows that adhesion molecule expression is induced or upregulated in affected tissues from patients with a wide variety of inflammatory diseases, including rheumatoid arthritis, atherosclerosis, multiple sclerosis, and diabetes 10, 11, 12. However, only a limited number of studies have investigated adhesion molecule expression in vasculitic disorders. These investigations have focused mainly in ICAM-1, VCAM-1, VLA-4, LFA-1, and Mac-1
In vitro model systems of human vasculitis
Specific mechanisms of leukocyte adhesion to endothelial monolayers have recently begun to be identified through the use of endothelial tissue culture techniques. Since the initial report by Jaffe et al (44) describing the culture of human venous endothelial cells from human umbilical veins, many studies have employed these and other types of endothelial cell cultures to understand better how the endothelium participates in immune responses and thrombotic states, and maintains its permselective
In vivo animal models of vasculitis
Although these in vitro studies have enhanced our understanding of how vasculitic lesion initiation and progression may occur, they are limited in that they cannot fully reproduce the pathophysiologic conditions that occur in vivo. Experimental animal model systems, such as the MRL/Mpj-Faslpr mice, NZB/NZW mice, and the Shwartzman and Arthus reactions have been used to elucidate the roles of adhesion molecules in the development of vasculitis (Table 3). Although these systems are valuable tools
Summary and future directions
Considerable experimental evidence has been reported to support the hypothesis that leukocyte–endothelial cell adhesion molecules are important mediators of tissue injury in a wide variety of inflammatory diseases. In comparison, the roles of adhesion molecules in the development of vasculitic diseases have only recently begun to be defined, and only a few adhesion molecules, such as ICAM-1 and VCAM-1, have been actively investigated. Comprehensive analyses that determine the expression and
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