Endothelial integrin

Fig. 20. Targeting of the endothelial integrin a P3 as a specific angiogenesis marker. The receptor is recognized by a biotinylated antibody that is then bound by an avidin moiety bearing a Gd(III) loaded liposome.

Integrins Mediate Adhesion of Neutrophils to Endothelial Cells... 

Adhesion of neutrophils to endothelial cells employs specific adhesive proteins (integrins) located on their surface and also specific receptor proteins in the endothelial cells. (See also the discussion of selectins in Chapter 47.)... 

Natalizumab (Tysabri ) is a recombinant humanized IgG4 mAb that binds to the a4-integrin subunit of a4(31 (VLA-4) and oA M (LPAM-1) integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the a4-mediated adhesion of leukocytes to their respective receptors.103 104 The receptor for a4pi, vascular cell adhesion molecule-1 (VCAM-1), is expressed on activated endothelial cells and is... 

These molecules interact with the leukocyte integrins and thus are important during the later stages of the inflammatory response, which are independent of selectin function. The major molecules present on endothelial cells are shown in Table 3.3. 

ICAM-1 and -2 are constitutively expressed on endothelial cells ICAM-1 may be further up-regulated by exposure to cytokines. ICAM-3 has recently been described (its identity based on the unique specificity of a monoclonal antibody) and is a 124-kDa glycoprotein present on the surfaces of T cells, monocytes and neutrophils its expression may be up-regulated by stimulants such as mitogens. VCAM-1, which is expressed on the luminal surface of cytokine-exposed endothelial cells, binds T cells via VLA-4. It is also expressed on the surface of some leukaemic cell lines, on rheumatoid synovial cells and on some tumours.On the other hand, ICAM-1 is found on all endothelial surfaces, and its interaction with neutrophil integrins is the major mechanism that results in the stimulation of transendothelial migration. 

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