Neutrophil integrins

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. 

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.)... 

Three subfamilies of integrins were recognized initially. Members of each subfamily were distinguished by containing a common (3 subunit, but they differed in their a subunits. However, more than three P subunits have now been identified, and the classification of integrins has become rather complex. Some integrins of specific interest with regard to neutrophils are fisted in Table 52-11. 

Table 52-11. Examples of integrins that are important in the function of neutrophils, of other white blood cells, and of platelets. ...

Neutrophils play a major role in the body s defense mechanisms. Integrins on their surface membranes determine specific interactions with various cell and tissue components. 

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... 

Beta-2 integrin Bottlenose dolphin, killer whales Activated neutrophils Species-specific [102]... 

After the initial attachment of neutrophils to the endothelium via the selec-tins, the next stage in the process is performed via the integrins. L-selectin on the neutrophil surface is shed (the shed molecule being some 8-10 kDa smaller than the bound molecule) via a process that probably involves proteolytic cleavage. The major groups of integrins present on leukocytes are shown in Table 3.2 further properties of these molecules are given later. 

Hickstein, D. D., Hickey, M. J., Ozols, J., Baker, D. M., Back, A. L., Roth, G. J. (1989). cDNA sequence for the aM subunit of the human neutrophil adherence receptor indicates homology to integrin a subunits. Proc. Natl. Acad. Sci. USA 86, 257-61. 

Diacovo TG, Roth SJ, Buccola JM, Bainton DF, Springer TA. Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CDllb/CD18. Blood 1996 88 146-157. 

T. Clustering of b2-integrins on human neutrophils activates dual signaling pathways to Ptdins 3-kinase. Exp. Cell Res., 256, 257-263 (2000)... 

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