Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 12, Issue 29, Pages 3799-3806Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138161206778559696
Keywords
autoimmune disease; integrin; leukocyte; endothelium; rolling; adhesion receptors; inflammation; antibody therapy
Categories
Ask authors/readers for more resources
The interaction of leukocytes with the vessel endothelium to facilitate the extravasation into the tissue represents a key process of the body's defense mechanisms. Excessive recruitment of leukocytes into the inflamed tissue in chronic diseases like autoimmune disorders could be prevented by interfering with the mechanisms of leukocyte extravasation. Significant progress in elucidating the molecular basis of the trafficking of leukocytes from the blood stream to the extravascular tissue has been achieved that enables new strategies for therapeutic approaches. The multistep process of leukocyte rolling, firm adhesion and transmigration through the endothelial wall is facilitated by a dynamic interplay of adhesion receptors on both leukocytes and endothelial cells as well as chemokines. In preclinical studies using various animal models, promising results have been received demonstrating that blocking of adhesion receptors of the selectin and integrin families improved the inflammation process in models of ulcerative colitis, autoimmune encephalomyelitis or contact hypersensitivity. In addition to the targeting of adhesion receptors by antibodies, small molecules that mimic epitopes of adhesion receptor ligands have been developed and successfully applied in animal models. Clinical studies revealed a limited response using antibodies to selectins or LFA-1 integrins compared with animal models. However, using humanized antibodies:to the alpha 4- integrin subunit significant efficacy has been demonstrated in autoimmune diseases like psoriasis, multiple sclerosis and inflammatory bowel disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available