Abstract. The leukocyte function-associated molecule-1 (LFA-1) plays a key role in cell adhesion processes between cells of the immune system. We investigated the mechanism that may regulate LFA-1-1igand interactions, which result in cell-cell adhesion. To this end we employed an intriguing anti-LFA-1 ot mAb (NKI-L16), capable of inducing rather than inhibiting cell adhesion. Aggregation induced by NKI-L16 or Fab fragments thereof is not the result of signals transmitted through LFA-1. The antibody was found to recognize a unique Ca2+-dependent activation epitope of LFA-1, which is essentially absent on resting lymphocytes, but becomes induced upon in vitro culture. Expression of this epitope correlates well with the capacity of cells to rapidly aggregate upon stimulation by PMA or through the TCR/CD3 complex, indicating that expression of the NKI-L16 epitope is essential for LFA-1 to mediate adhesion. However, expression of the NKI-L16 epitope in itself is not sufficient for cell binding since cloned T lymphocytes express the NKI-L16 epitope constitutively at high levels, but do not aggregate spontaneously. Based on these observations we propose the existence of three distinct forms of LFA-I: (a) an inactive form, which does not, or only partially exposes the NKI-L16 epitope, found on resting cells; (b) an intermediate, NKI-L16 ÷ form, expressed by mature or previously activated cells; and (c) an active (NKI-L16 ÷) form of LFA-1, capable of high affinity ligand binding, obtained after specific triggering of a lymphocyte through the TCR/CD3 complex, by PMA, or by binding of NKI-L16 antibodies.
Please be advised that this information was generated on 2018-05-09 and may be subject to change.Eur. J. Im m unol. 1987Im m unol. .17:1317Im m unol. -1322 Role of pl50,95 in monocyte adhesion-associated processes 1317
migration, chemotaxis human monocytesThe leukocyte function-associated antigen-1 (LFA-1), the C3bi receptor (CR3) and the p i50,95 antigen belong to a family of leukocyte surface molecules consisting of bimolecular complexes with a chains of 170 kDa, 165 kDa and 150 kDa, respectively, and a common [ 3 > subunit with a mol. mass of 95 kDa. In order to determine the function of the pl50,95 antigen on human monocytes and U937 cells, and to study the functional relationship between this antigen and LFA-1 or CR3, we investigated the influence of monoclonal antibodies (mAb) directed against these cell surface molecules on the adhesive properties of these cells. The observation that anti-|3 chain mAb strongly inhibited migration, chemotaxis, adhesion and phagocytosis of mono cytic cells indicates a major role for LFA-1 family antigens in monocyte functions. Detailed analysis with a panel of anti-a chain antibodies demonstrated that both pl50,95 and LFA-1 mediate random migration whereas in contrast, pl50,95 and CR3 were shown to be involved in the directed migration of monocytes to f-Met~Leu-Phe. Furthermore, adhesion of monocytes to plastic surfaces or monolayers of endothelial cells as well as phagocytosis of latex particles was mediated by pl50,95. The results demonstrate that, in spite of its relative low expression, the pl50,95 glycoprotein is a major adhesion-associated molecule expressed by human monocytic cells.
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