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Lymphocytes adhere to cells or extracellular matrices to perform functions relating to cytotoxicity, extravasation and tissue localization, as well as modulation of lymphocyte growth and maturation. This adherence is mainly mediated by 3 families of cell-surface adhesion molecules: integrins, immunoglobulin-related molecules and selectins. Since variations in the degree of adherence may affect the pathophysiology of lymphoproliferative disorders, the expression of a large number of adhesion molecules was analysed on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs), and on EBV-positive or EBV-negative Burkitt's lymphoma (BL) lines, by immunofluorescence flow cytometry and immunoprecipitation with monoclonal antibodies. With regard to the beta 1, beta 2 and beta 3 integrin subfamilies, LCLs strongly expressed CD49d/CD29 (VLA-4), CD11a/CD18 (Leu-CAMa, LFA-1) and CD51/CD61 (vitronectin receptor). These cells also abundantly expressed CD54 (ICAM-1) and CD58 (LFA-3) as well as the "homing receptors" L-selectin (LECAM-1) and CD44. BL lines had considerably lower amounts of VLA-4 than LCLs, and ICAM-1 was expressed only by some of the tumor lines. All other adhesion molecules were absent or minimally expressed in the BL cells.

Monocyte/macrophages adhere to cells (lymphocytes, vascular endothelial and other cell types) and to extracellular matrix components (fibronectin and laminin) by using specific cell surface adhesive structures. In the present study we have analyzed expression of integrins, immunoglobulin (Ig)-related, selectins, and other adhesion molecules on blood monocytes, in vitro differentiated macrophages (ivMs), and alveolar macrophages (AMs), obtained from healthy nonsmokers by bronchoalveolar lavage (BAL). We have also investigated expression of adhesion molecules on myelomonocytic cell lines HL-60, THP-1, KG-1, and U937 before and after tetradecanoyl phorbol acetate (TPA)-induced differentiation. With regard to the integrin family, monocytes expressed beta 1 (CD29), alpha 4, alpha 5, alpha 6, beta 2 (CD18), CD11a, CD11b, and CD11c subunits, but not alpha V (CD51). Some reactivity with mAbs against the platelet antigens CD41b (IIb) and CD61 (beta 3) was detected. The Ig-related molecules CD54 (ICAM-1), ICAM-2, and CD58 (LFA-3) were expressed, as well as L-selectin and the carbohydrate ligands Le(x) (CD15) and sialyl Le(x). Immunolabeling for the structurally unrelated molecules CD44 and CD36 was strongly positive. In comparison to monocytes, AMs showed much lower expression of alpha 4, alpha 6, beta 2, CD11a, CD11b, L-selectin, Le(x), and sialyl Le(x). Moreover, ICAM-2 and CD36 were practically absent whereas expression of alpha 3, but not of CD11c, was higher. Similar results were obtained with ivMs. All four myelomonocytic cell lines showed down-regulation of alpha 4 and up-regulation of CD11c after TPA treatment. These findings indicate that maturation of monocytes into macrophages is accompanied by characteristic changes in adhesion molecule expression. The particular array of adhesion molecules on monocytes and macrophages may account for differences in the functional properties of these cells.

Insulin-dependent diabetes mellitus (IDDM) results from a T cell-dependent autoimmune destruction of insulin-producing pancreatic beta cells. In the present study, expression of adhesion molecule ICAM-1 (CD54) on pancreatic beta cells was studied in normal, obese hyperglycemic (ob/ob), and nonobese diabetic (NOD) mice. Freshly isolated pancreatic beta cells from ob/ob mice did not express ICAM-1, but treatment of the cells with IL-1-beta, TNF-alpha, or INF-gamma strongly induced its expression as measured by immunofluorescence flow cytometry. The cytokines acted in a dose- and time-dependent manner. Maximal induction by either cytokine occurred at 24 hr and thereafter expression decreased, except for INF-gamma. Immunoprecipitation from IL-1-beta-treated beta cells demonstrated a cell-surface glycoprotein with an apparent molecular weight of 95 kDa. ICAM-1 expression was undetectable on pancreatic beta cells of normal and ob/ob mice as measured by immunohistochemistry. In NOD mice at different ages (1 to 6 months) ICAM-1 was also undetectable on beta cells, in contrast to the strong expression on infiltrating mononuclear cells. The present study indicates that mouse pancreatic beta cells, under certain conditions, can express ICAM-1.

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.

Leukocyte adhesion to cells is mediated by the cell-surface glycoprotein complex CDIIa-c/CD18 and, in some cases, the glycoprotein gp84. The process is associated with leukocyte activation and modulates lymphocyte proliferation and maturation. Epstein-Barr virus (EBV)-transformed normal B lymphocytes give rise to lymphoblastoid cell fines (LCLs) which grow as large clusters mediated by adhesion molecules. In contrast, newly explanted EBV-infected Burkitt lymphoma (BL) cells usually grow as single cells or as loose clusters. We now report that EBV positive- and EBV-negative BL lines lack the adhesive protein complex, or have only low levels of it, whereas LCLs, representing various stages of B-lymphocyte development, contain considerably higher amounts, as measured by immunofluorescence flow cytometry and immuno precipitation. The level of gp84 expression is of the same magnitude in both types of cells.

Monoclonal antibody LB-2 to a surface antigen on human B cells, lymphoblast, monocytes and vascular endothelial cells largely inhibited adhesion among Epstein Barr virus-immortalized normal B cells (EBV-B) and concanavalin A-stimulated blood mononuclear cells (Con A-BMC) before and after phorbol ester treatment. The antibody inhibited to a lesser extent phorbol ester-induced aggregation of monocytes, U937 cells and fresh BMC and had virtually no inhibitory effect on the adhesion among enriched T cells and granulocytes. A surface glycoprotein band of 84 kDa was obtained from EBV-B cells by immunoprecipitation and gel electrophoresis. Immunological and biochemical studies clearly distinguished this molecule from gp90 and associated glycoproteins which also mediate leukocyte adhesion.

In humans, lymphocyte adhesion to cells is mediated by the protein heterodimer CD11a/CD18 (Leu-CAMa, LFA-1) and its ligand CD54 (ICAM-1). Although the murine CD11a/CD18 is well characterized, the mouse homologue of human ICAM-1 has not been identified. In the present study a rat monoclonal antibody to the murine lymphocyte activation antigen MALA-2 was found to inhibit in a dose-dependent manner the phorbol ester-enhanced aggregation of mouse lymphoblasts, an adhesion-specific assay, and hence to define an adhesion molecule. By immunofluorescence flow cytometry the antigen expression was low on spleen cells but it largely increased after stimulation with mitogens. The antigen was expressed by some, but not all, lymphoid cell lines, and myelomonocytic and mastocytoma cells were also positive. In frozen tissue sections MALA-2 was mainly detected on germinal center B cells, dendritic cells, macrophages and vascular endothelium, including high endothelial venules. Cell surface labeling followed by immunoprecipitation and gel electrophoresis indicated that the antigen is a sialoglycoprotein which has a relative molecular mass of 95 kDa and displays a faster electrophoretic mobility under non-reducing conditions. The function, cellular distribution and molecular properties of MALA-2 are indistinguishable from those of human ICAM-1.