The beta 2-integrin CD11a/CD18 binds to the intercellular adhesion molecules (ICAM)-1 (CD54) and ICAM-2. ICAM-1 has a wide distribution, and its expression is up-regulated by various cytokines. In contrast, ICAM-2 has a more restricted distribution, and is mainly expressed on endothelial cells. In the present study we show that it is not induced by inflammatory cytokines or other treatments on any of several cells studied. Moreover, antibodies to the intercellular adhesion ligands were not able to block all CD11a/CD18-dependent adhesion, indicating the presence of additional CD11a/CD18 ligands.

The leucocyte surface glycoproteins CD11a (gp160, LFA-1 antigen, TA-1 antigen), CD11b (gp155, Mac-1 antigen, OKM1 antigen, Mo-1 antigen), CD11c (gp130, Leu-M5 antigen), and CD18 (gp90) constitute three heterodimers with different alpha chains and a common beta chain. Monoclonal antibodies to CD11a, b, or c block adhesion of certain types of leucocytes only, while several antibodies to CD18 inhibit adhesion in all of them. The functionally important site or sites on CD18 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.

Abstract. ~2 integrin (CDlla,b,c/CD18)-mediated cell adhesion is required for many leukocyte functions. Under normal circumstances, the integrins are nonadhesive, and become adhesive for their cell surface ligands, the intercellular adhesion molecules (ICAMs), or soluble ligands such as fibrinogen and iC3b, when leukocytes are activated. Recently, we defined a peptide derived from ICAM-2, which specifically binds to purified CDlla/CD18. Furthermore, this peptide strongly induces T cell aggregation mainly mediated by CDlla/CD18-ICAM-1 interaction, and natural killer cell cytotoxicity. In the present study, we show that the same ICAM-2 peptide also avidly binds to purified CDllb/CD18, but not to CDllc/CD18. This binding can be blocked by the CD1 lb antibody OKM10. The peptide strongly stimulates CDllb/CD18-ICAM-l-mediated cell aggregations of the monocytic cell lines THP-1 and U937. The aggregations are energy and divalent cation-dependent. The ICAM-2 peptide also induces CDllb/CD18 and CDllc/CD18-mediated binding of THP-1 cells to fibrinogen and iC3b coated on plastic. These findings indicate that in addition to induction of CDlla/CD18-mediated cell adhesion, the ICAM-2 peptide may also serve as a "trigger" for high avidity ligand binding of other ~2 integrins.

Intravascular malignant lymphomatosis (IML) is a highly malignant, recently recognized form of lymphoma. It is characterized by multifocal proliferation of malignant lymphocytes within small blood vessels, primarily in the central nervous system and skin, frequently resulting in circulatory disturbances. The cause of the impaired capability of the malignant lymphocytes to extravasate has remained unclear. We analyzed the presence of immunoreactivity for certain homing receptor and adhesion molecules associated with lymphocyte extravasation in 3 patients with this disease. Compared with non-neoplastic leukocytes, large malignant lymphocytes appeared either negative or only weakly positive for the leukocyte surface glycoprotein, CD18 that is the beta chain of the CDIIa/CD18 complex (lymphocyte-function associated antigen-I, LFA-I), which mediates cell-to-cell adhesion of lymphocytes. On the other hand, antibody to one of the proposed ligands for this complex, intercellular adhesion molecule-I, gave positive reactivity both on lymphocytes and on endothelial cells. Further, the malignant lymphoid cells stained positively with Hermes-3 antibody, which recognizes a common structure of CD44 class of molecules involved in lymphocyte homing. It was also shown that HECA-452 antigen, a marker of high endothelial venules (HEV) supporting lymphocyte extravasation, can be synthesized by an IML patient even at the site of inflammation but it is not prerequisite for extravasation of inflammatory lymphocytes. Our results suggest that the deficiency or absence of the adhesion molecule CDIIa/CD18 may contribute to the inability of the malignant lymphoid cells to extravasate in IML, and perhaps also to the high malignancy of this form of lymphoma.