Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member.

Human CD38 is a cell surface molecule involved in the regulation of lymphocyte adhesion to endothelial cells. This suggests that HUVEC bear a ligand(s) for CD38 on the cell surface. By means of the mAb Moon-1, which specifically inhibits CD38-mediated cell adhesion, we have identified a trans-membrane 130-kDa molecule acting as a ligand for CD38. Here, we report that the molecule recognized by the Moon-1 mAb is CD31, a member of the Ig superfamily. This conclusion is based on 1) cross-inhibition assays between Moon-1 and reference anti-CD31 mAbs; 2) sequential immunoprecipitation experiments using Moon-1 and known anti-CD31 mAbs, and 3) reactivity of the Moon-1 mAb with CD31 transfectants. Further, CD31 and CD38 cognate interactions were found to modulate heterotypic adhesion as well as to implement cytoplasmic calcium fluxes identical to those obtained by means of agonistic anti-CD38 mAbs. Other effects tested included the synthesis of messages for a panel of cytokines, markedly increased upon receptor-ligand interactions. These results suggest that the interplay between CD38 and its ligand CD31 is an important step in the regulation of cell life and of the migration of leukocytes (and CD38+ cancer cells) through the endothelial cell wall.

[1]  F. Malavasi,et al.  Human CD38, a leukocyte receptor and ectoenzyme, is a member of a novel eukaryotic gene family of nicotinamide adenine dinucleotide+-converting enzymes: extensive structural homology with the genes for murine bone marrow stromal cell antigen 1 and aplysian ADP-ribosyl cyclase. , 1997, Journal of immunology.

[2]  S. Hoshino,et al.  Mapping of the catalytic and epitopic sites of human CD38/NAD+ glycohydrolase to a functional domain in the carboxyl terminus. , 1997, Journal of immunology.

[3]  A. Pileri,et al.  Selective induction of CD73 expression in human lymphocytes by CD38 ligation: a novel pathway linking signal transducers with ecto-enzyme activities. , 1996, Journal of immunology.

[4]  A. la Sala,et al.  Secretion of IFN-gamma, IL-6, granulocyte-macrophage colony-stimulating factor and IL-10 cytokines after activation of human purified T lymphocytes upon CD38 ligation. , 1996, Cellular immunology.

[5]  F. Malavasi,et al.  Identification and characterization of an active soluble form of human CD38 in normal and pathological fluids. , 1996, International immunology.

[6]  D. McRee,et al.  Crystal structure of Aplysia ADP ribosyl cyclase, a homologue of the bifunctional ectozyme CD38 , 1996, Nature Structural Biology.

[7]  F. Malavasi,et al.  Human CD38, a cell‐surface protein with multiple functions , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  M. Reth,et al.  Signaling through CD38 augments B cell antigen receptor (BCR) responses and is dependent on BCR expression. , 1996, Journal of immunology.

[9]  C. Arrieumerlou,et al.  Coordinated regulation in human T cells of nucleotide-hydrolyzing ecto-enzymatic activities, including CD38 and PC-1. Possible role in the recycling of nicotinamide adenine dinucleotide metabolites. , 1996, Journal of immunology.

[10]  W. Knapp,et al.  Interaction of CD31 with a heterophilic counterreceptor involved in downregulation of human T cell responses , 1996, The Journal of experimental medicine.

[11]  F. Malavasi,et al.  Expression of cyclic ADP-ribose-synthetizing CD38 molecule on human platelet membrane. , 1996, Blood.

[12]  E. Brown,et al.  Identification of αvβ3 as a heterotypic ligand for CD31/PECAM-1 , 1996 .

[13]  J. Banchereau,et al.  Human CD38 ligand. A 120-KDA protein predominantly expressed on endothelial cells. , 1996, Journal of immunology.

[14]  D. Campana,et al.  CD38 signal transduction in human B cell precursors. Rapid induction of tyrosine phosphorylation, activation of syk tyrosine kinase, and phosphorylation of phospholipase C-gamma and phosphatidylinositol 3-kinase. , 1996, Journal of immunology.

[15]  E. Brown,et al.  Identification of αvβ3 as a heterotypic ligand for CD31/PECAM-1 , 1996 .

[16]  D. Födinger,et al.  High expression of a CD38-like molecule in normal prostatic epithelium and its differential loss in benign and malignant disease. , 1995, The Journal of urology.

[17]  C. Uherek,et al.  CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium , 1995, The Journal of cell biology.

[18]  G. Maul,et al.  Molecular characterization of NDP52, a novel protein of the nuclear domain 10, which is redistributed upon virus infection and interferon treatment , 1995, The Journal of cell biology.

[19]  H. DeLisser,et al.  Molecular and functional aspects of PECAM-1/CD31. , 1994, Immunology today.

[20]  A. Barclay,et al.  Transient intercellular adhesion: the importance of weak protein-protein interactions. , 1994, Trends in biochemical sciences.

[21]  U. Dianzani,et al.  Interaction between endothelium and CD4+CD45RA+ lymphocytes. Role of the human CD38 molecule. , 1994, Journal of immunology.

[22]  S. Zupo,et al.  CD38 signaling by agonistic monoclonal antibody prevents apoptosis of human germinal center B cells , 1994, European journal of immunology.

[23]  P. Newman,et al.  The Role of PECAM‐1 in Vascular Cell Biology a , 1994, Annals of the New York Academy of Sciences.

[24]  F. Malavasi,et al.  Human CD38: a glycoprotein in search of a function. , 1994, Immunology today.

[25]  J. Bazan,et al.  Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. , 1993, Science.

[26]  D. Phillips,et al.  PECAM-1 is required for transendothelial migration of leukocytes , 1993, The Journal of experimental medicine.

[27]  H. DeLisser,et al.  Platelet/endothelial cell adhesion molecule-1 (CD31)-mediated cellular aggregation involves cell surface glycosaminoglycans. , 1993, The Journal of biological chemistry.

[28]  E. Koonin.  A new group of putative RNA helicases. , 1992, Trends in biochemical sciences.

[29]  D. States,et al.  Similarities in amino acid sequences of Aplysia ADP-ribosyl cyclase and human lymphocyte antigen CD38. , 1992, Trends in biochemical sciences.

[30]  H. DeLisser,et al.  A heterophilic adhesion mechanism for platelet/endothelial cell adhesion molecule 1 (CD31) , 1992, The Journal of experimental medicine.

[31]  U. Dianzani,et al.  CD38: A multi-lineage cell activation molecule with a split personality , 1992, International journal of clinical & laboratory research.

[32]  O. Majdic,et al.  Molecular characterization and functional analysis of the leukocyte surface protein CD31. , 1990, Journal of immunology.

[33]  M. Zaccolo,et al.  Involvement of the multilineage CD38 molecule in a unique pathway of cell activation and proliferation. , 1990, Journal of immunology.

[34]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[35]  J. Gorski,et al.  PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. , 1990, Science.

[36]  Hon Cheung Lee,et al.  Structural determination of a cyclic metabolite of NAD+ with intracellular Ca2+-mobilizing activity. , 1989, The Journal of biological chemistry.

[37]  A. Bernard,et al.  Human leukocyte differentiation antigens. , 1984, Journal of immunology.

[38]  G. Camussi,et al.  Antibody-induced redistribution of Heymann antigen on the surface of cultured glomerular visceral epithelial cells: possible role in the pathogenesis of Heymann glomerulonephritis. , 1985, Journal of immunology.

[39]  F. Malavasi,et al.  Characterization of a murine monoclonal antibody specific for human early lymphohemopoietic cells. , 1984, Human immunology.

[40]  L. Hillestad,et al.  Acute promyelocytic leukemia. , 2009 .