Pekka Nortamo

Immunological Mapping of the Human Leucocyte Adhesion Glycoprotein gp90 (CD 18) by Monoclonal Antibodies

The leucocyte surface glycoproteins CD11a (gp160, LFA‐1 antigen, TA‐1 antigen), CD11b (gp155, Mac‐1 antigen, Mo‐1 antigen), CD11c (gp 130, Leu‐M5 antigen), and CD18 (gp90) constitute three heterodimers with different α chain and a common β chain Monoclonal antibodies to CD11a, b, or c block adhesion of certain types of leucocytes only, while several antibodies to CD 18 inhibit adhesion in all of them. The functionally important site or sites on CD 18 are not known. We have now isolated the CD11a,b,c‐CD18 leucocyte antigen complex in large amounts from human leucocytes, and produced several new monoclonal antibodies reacting with CD18. One of these antibodies, like those described earlier, inhibits leucocyte adhesion, whereas the others do not. By means of competition experiments, at least four epitope regions were found. These antibodies should be valuable in elucidating the regions essential in CD18‐mediated leucocyte functions.

Rabbit leukocyte adhesion molecules CD11CD18 and their participation in acute and delayed inflammatory responses and leukocyte distribution in vivo

In humans the glycoprotein complexes CD11/CD18 mediate leukocyte adhesion to cells. Mouse monoclonal antibodies (mAb) 60.3, 7E4, and IB4 to human CD18, found to cross-react with rabbit white blood cells, were used to identify the antigen in rabbit cells and to study adherence of rabbit leukocytes in vitro and in vivo. These antibodies labeled almost all unfractionated rabbit blood leukocytes and immunoprecipitated surface glycopolypeptides with apparent molecular weights of 85,000 and 150,000 from these cells. Adhesion of purified rabbit polymorphonuclear cells (PMNs) to cultured vascular endothelial cells in the presence of phorbol ester was blocked by the antibodies in a dose-dependent manner. The acute inflammatory response characterized by local accumulation of PMNs and concomitant plasma extravasation following intradermal injections of zymosan-activated serum (ZAS) in rabbits was inhibited in animals pretreated intravenously with anti-CD18 mAb. Intravital microscopy of the rabbit tenuissimus muscle demonstrated that anti-CD18 mAb. Intravital microscopy of the rabbit tenuissimus muscle demonstrated that anti-CD18 treatment specifically blocked the adhesion of activated leukocytes to the venular endothelium and thereby the subsequent diapedesis of these cells into the extravascular space. The lymphocyte-dependent tissue swelling resulting from a delayed-type hypersensitivity reaction in the rabbit ear was partially inhibited by anti-CD18 mAb. Systemic anti-CD18 treatment induced a pronounced increase in the number of circulating mononuclear and polymorphonuclear cells with a maximum at 24 hr after injection of the antibody. It is concluded that GP150/GP85 is the rabbit homologue of human CD11/CD18, and that leukocyte-cell adhesion mediated by these glycoprotein complexes participates in acute and delayed inflammatory responses and leukocyte distribution in vivo.

The pivotal role of the Leu-CAM and ICAM molecules in human leukocyte adhesion

Cellular adhesion is of fundamental importance in leukocyte physiology. It is a complex, strictly regulated process, which involves the participation of several cell surface glycoproteins. Among the most important are the Leu-CAMs or the CD11/CD18 integrin receptors, and their adhesion ligands ICAM-1 (CD54) and ICAM-2. In this review we summarize some recent work on various aspects of these molecules.

Leukocyte Cell Adhesion Proteins: from Molecular Dissection to Clinical Applications

Leukocyte adhesion is needed for a number of leukocyte functions like immunoglobulin synthesis, T and NK-cell-mediated cytotoxicity, phagocytosis by granulocytes, and cellular accumulation in inflamed tissue. Several cell surface molecules involved in leukocyte-leukocyte and leukocyte-target cell interactions have recently been identified and characterized. Both the polypeptide and carbohydrate portions are important in leukocyte interactions. It is becoming increasingly apparent that it is possible to interfere with the normal functions of the leukocyte adhesion glycoproteins, and such applications may become important in medicine.