
Description
CD11a (LFA-1 alpha) together with CD18 constitute leukocyte function-associated antigen 1 (LFA-1), the alphaLbeta2 integrin. CD11a is implicated in activation of LFA-1 complex. LFA-1 is expressed on the plasma membrane of leukocytes in a low-affinity conformation. Cell stimulation by chemokines or other signals leads to induction the high-affinity conformation, which supports tight binding of LFA-1 to its ligands, the intercellular adhesion molecules ICAM-1, -2, -3. LFA-1 is thus involved in interaction of various immune cells and in their tissue-specific settlement, but participates also in control of cell differentiation and proliferation and of T-cell effector functions. Blocking of LFA-1 function by specific antibodies or small molecules has become an important therapeutic approach in treatment of multiple inflammatory diseases. For example, humanized anti-LFA-1 antibody Efalizumab (Raptiva) is being used to interfere with T cell migration to sites of inflammation; binding of cholesterol-lowering drug simvastatin to CD11a allosteric site leads to immunomodulation and increase in lymphocytic cholinergic activity.
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