Endothelial leukocyte adhesion molecule-1 ELAM

Whelan, J., Ghersa, P., Hooft van Huijsduijnen, R., Gray, J., Chandra, G., Talabot, F., and DeLamarter, J. F. (1991). An NFKB-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription. Nucleic Acids Res. 19, 2645-2653. 

Upregulation of adhesion molecules has been documented in human stroke patients [7]. It was demonstrated that leukocytes from patients suffering an ischemic stroke or transient ischemic attack showed increased CDl la expression within 72 hours of the onset of symptoms [123]. Increased ICAM-1 expression on the surface of vessels fi om cerebral cortical infarcts was detected in four patients [124]. In some studies, soluble isoforms of adhesion molecules shed fi om the surfaces of activated cells were quantified in serum. Serum endothelial-leukocyte adhesion molecule-1 (ELAM-1, E-selectin) levels increased up to 24 hours after stroke. Similar increases were observed in serum vascular cell adhesion molecule-1 (VCAM-1) levels and these increases were sustained up to 5 days [125]. In contrast, serum ICAM-1 levels in acute ischemic stroke patients have been found to be lower than or the same as those of asymptomatic control subjects matched for age, sex, and vascular risk factors [125,126]. The reason not to detect an increase in serum levels of adhesion molecules might be due to the late enrolling of patients. Once adhesion molecules bind to leukocytes and endothelial cells, they can no longer be detected in serum [7]. 

Montefort, S., Roche, W.R, Howarth, P.H., Djukanovic, R, Gratziou, C., Carroll, M., Smith, L., Britten, K.M., Haskard, D., Lee, T.H. and Holgate, S.T. (1992). Intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects. Eur. Respir. J. 5, 815-823. 

The innervation of the lymphoid vasculature by substance P-containing neurons and the ability of substance P to enhance lymph tissue blood flow (Lundbeig et al., 1985) suggest that substance P may alter lymphocyte traffic . Substance P induces the expression of endothelial leukocyte adhesion molecule 1 (ELAM-1) on microvascular endothelial cells (Matis et al., 1990) and may similarly affect the expression of adhesion molecules on lymphocytes. Infusion of substance P has been shown to increase lymph flow and lymphocyte traffic in sheep lymph nodes (Moore etal., 1989). 

Increased cytokine production may also play a role in silica-induced autoimmune vascular disease. Adhesion molecule expression is elevated on vascular endothelial cells in response to TNF-a and IL-1. Adhesion molecules such as endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) recruit inflammatory cells to specific sites on the vascular endothelium, and it has been hypothesized that vascular pathology following silica exposure may be the result of this interaction (Nowack et al., 1998). IFN-y is expressed at elevated levels by lymphocytes in silicotic thoracic lymph nodes and may be responsible for the long-lasting inducible nitric oxide synthase (iNOS) expression in these tissues (Friedetzky et al., 2002). The increase in IFN-y may also cause a shift towards a dominant Thl response, contributing to the maintenance of a chronic inflammatory state in silica-containing lymph nodes (Gam et al., 2000). 

Selectins constitute a family of mammalian, carbohydrate-binding membrane ycoproteins present in leukocytes and endothelium. Three members of the family are well characterized leukocyte homing receptor (LAM-1, L-selectin), endothelial leukocyte adhesion molecule (ELAM-1, E-selectin), and CD62 (P-selectin) of platelets. All three have an N-terminal extracellular domain of 117-120 amino acid residues, which is responsible for Ca -dependent carbohydrate recognition. This is followed by an epidermal owth factor-like domain of 34-40 amino acids, in turn followed by variable numbers of 62-amino acid consensus repeats. There is then a transmembrane segment and a cytoplasmic domain. 

Berg, E. L., Robinson, M. K., Mansson, 0., et al. A carbohydrate domain common to both sialyl Le(a) and sialyl Le(X) is recognized by the endothelial cell leukocyte adhesion molecule ELAM-1. J. Biol. Chem. 266 14869-14872, 1991. 

GMP, granular membrane protein ODFR, oxygen-derived free radicals ELAM, endothelial leukocyte adhesion molecule IL-1, interleukin-1 TNF-alpha, tumor necrosis factor-alpha ICAM, intercellular adhesion molecule IFN-gamma, interferon -gamma VCAM, vascular cell adhesion molecule LFA, lymphocyte-associated antigen CR, complement receptor. 

M. J. Polley, M. L. Phillips, E. Wayner, E. Nudelman, A. K. Singhal, S. Hakomori, and J. C. Paulson, CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis X, Proc. Natl. Acad. Sci. USA 88 6224 (1991). 

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