G.D. Keizer

On the mode of action of LFA-1

Abstract The leukocyte function-associated molecule 1 (LFA-1) plays a key role in cell adhesion among leukocytes and between leukocytes and other cell types. Although two ligands of LFA-1 have been identified, namely the intercellular adhesion molecules 1 (ICAM-1) and 2 (ICAM-2), the exact mechanism by which LFA-1 binds to and detaches from its ligand(s) has remained obscure. Based on novel findings Carl Figdor, Yvette van Kooyk and Gerrit Keizer now present a model of LFA-1-mediated lymphocyte adhesion, showing that LFA-1-dependent cell adhesion is a dynamic process in which ligand-binding affinity is regulated by intramolecular changes in LFA-1. This process is controlled by other lymphocyte surface structures, notably CD2 and CD3.

Sensitive and quantitative determination of monocyte adherence.

A new sensitive and highly reproducible one-step ELISA is described to quantitatively determine the adherent capacity of monocytes and related cell lines. Cells were labelled with a monoclonal antibody/peroxidase conjugate which did not affect the adhesive properties of these cells. The labelled cells were allowed to adhere for 1 h and subsequently stained by the addition of substrate. The results demonstrate that there is a good correlation between the number of peroxidase-labelled adherent cells and the absorbance measured at 450 nm. Furthermore the assay permits the use of very low cell numbers since adherent cells could be measured efficiently at a level of only 100-500 cells/well. The method may be very useful in the selection of hybridomas that secrete antibodies which inhibit adherence of cells. In addition it can be applied to study the adhesive properties of any cell type, provided that appropriate monoclonal antibodies are available.

MEL-14 and LFA-1, Organ Specific and Non-Specific Adhesion Molecules Involved in Homing of Human Lymphocytes

In the process of recirculation lymphocytes migrate from the blood into the surrounding tissues by adhering to and crossing the wall of high endothelial venules (1–4). Recently we and others have provided evidence that in man, like in rodents, a system of organ-specific receptors mediates lymphocyte-HEV recognition and thus presumably controls lymphocyte homing to lymphoid tissues and sites of inflammation (4–7).