Expression of leucocyte and lymphocyte adhesion molecules in the human kidney (original) (raw)
1989, Kidney International
Expression of leucocyte and lymphocyte adhesion molecules in the human kidney. Leucocyte interaction with other cells is facilitated by the adhesion molecules, leucocyte function-associated antigen-I (LFA-1)-binding to intercellular adhesion molecule-! (ICAM-!) and for T cells and natural killer (NK) cells the binding of LFA-2 (CD2) to LFA-3. As these interactions are critical for the mediation of graft destruction by effector T cells, we examined whether there was a change in the expression of these molecules during rejection compared to normal kidneys. In normal kidneys, peritubular and glomerular capillaries and large vessel endothelium expressed ICAM-l and LFA-3, but tubular cells expressed only low levels of LFA-3. LFA-l-expressing cells, which were probably macrophages, were observed in the glomerulus. A few scattered LFA-l-expressing cells in the interstitium were probably tissue macrophages or dendritic cells, and only occasional interstitial mononuclear cells expressed LFA-2. During rejection, there was an infiltrate of mononuclear cells expressing LFA-I and the T cell and NK cell component of the infiltrate expressed LFA-2. Neither of these markers was expressed by kidney parenchymal cells except for one allograft with severe rejection which showed LFA-1 beta chain expression by some tubular cells. Tubular cells had increased expression of ICAM-l during rejection but there was no increase in LFA-3. The importance of LFA-2 and ICAM-l expression on kidney tubular cells for adhesion of activated T cells was also examined in an in vitro system. An assay of binding of lymphocytes to monolayers of cultured kidney (HK) cells showed that there was greater adhesion of immuneactivated lymphocytes to kidney cells (37.4 4.6% bound) than resting lymphocytes (14.3 3.5%), and this adhesion was inhibited by antibody to LFA-l (59,0 10.1% inhibition) and ICAM-l (34.9 4.4%) but not to LFA-2 or LFA-3. These results suggest that adhesion of lymphocytes to HK cells is mediated mainly by a LFA-l-dependent pathway. As kidney microvasculature constitutively expresses both adhesion molecules and HLA class I and class II, it is likely that these cells are the initial targets of effector cells of rejection and are preferentially destroyed. Increased expression of ICAM-l and HLA antigens on tubular cells with rejection will also increase their interaction with effector cells and make them more vulnerable to destruction. Adhesion molecules are essential for non-specific binding between leukocytes and in the binding of leukocytes to cells of non-leukocyte origin. Two complementary sets of adhesion molecules have been identified. Leukocyte function-associated-1 (LFA-1) is a heterodimer of a 180 kD alpha chain and a 95 kD beta chain, the latter being common to LFA-i, Mac-i and p150,95 [reviewed in 1]. LFA-l has been shown to be expressed
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