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© The Rockefeller University Press, 0021-9525/1997//421 $5.00
The Journal of Cell Biology, Volume 136, Number 2, , 1997 421-431

Article

Differential Regulation and Function of CD73, a Glycosyl-Phosphatidylinositol–linked 70-kD Adhesion Molecule, on Lymphocytes and Endothelial Cells



Laura Airas, Jussi Niemelä, Marko Salmi, Tarja Puurunen, David J. Smith, and Sirpa Jalkanen

National Public Health Institute and MediCity Research Laboratory, Turku University, 20520 Turku, Finland

CD73, otherwise known as ecto-5'-nucleotidase, is a glycosyl-phosphatidylinositol–linked 70-kD molecule expressed on different cell types, including vascular endothelial cells (EC) and certain subtypes of lymphocytes. There is strong evidence for lymphocyte CD73 having a role in several immunological phenomena such as lymphocyte activation, proliferation, and adhesion to endothelium, but the physiological role of CD73 in other cell types is less clear. To compare the biological characteristics of CD73 in different cell types, we have studied the structure, function, and surface modulation of CD73 on lymphocytes and EC. CD73 molecules on lymphocytes are shed from the cell surface as a consequence of triggering with an antiCD73 mAb, mimicking ligand binding. In contrast, triggering of endothelial CD73 does not have any effect on its expression. Lymphocyte CD73 is susceptible to phosphatidylinositol phospholipase, whereas only a small portion of CD73 on EC could be removed by this enzyme. Furthermore, CD73 on EC was unable to deliver a tyrosine phosphorylation inducing signal upon mAb triggering, whereas triggering of lymphocyte CD73 can induce tyrosine phosphorylation. Despite the functional differences, CD73 molecules on lymphocytes and EC were practically identical structurally, when studied at the protein, mRNA, and cDNA level. Thus, CD73 is an interesting example of a molecule which lacks structural variants but yet has a wide diversity of biological functions. We suggest that the ligand- induced shedding of lymphocyte CD73 represents an important and novel means of controlling lymphocyte– EC interactions.

Abbreviations used in this paper: EC, vascular endothelial cells; ecto-5'NT, CD73/ecto-5'-nucleotidase; GPI, glycosyl-phosphatidylinositol; HUVEC, human umbilical vein endothelial cells; IF, immunofluorescence; MFI, mean fluorescence intensity; PBL, peripheral blood lymphocytes; PI-PLC, phosphatidylinositol-specific phospholipase C.

Please address all correspondence to Laura Airas, MediCity Research Laboratory, Tykistökatu 6A, 20520 Turku, Finland. Tel.: 358-2-333-7001; Fax: 358-2-333-7000.


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