Human CD38 ligand. A 120-KDA protein predominantly expressed on endothelial cells.
Human CD38, a pleiotropic molecule with ADP-ribosyl cyclase activity, regulates activation and growth of several cell types. Its in vivo function is incompletely determined, mainly due to the lack of evidence concerning the existence of a single or multiple ligands. We recently observed that CD38 rules a selectin-type adhesion between lymphoid cells and HUVECs. A panel of murine mAbs raised against HUVEC included one (Moon-1) constantly blocking the CD38-mediated adhesion of several cell lines to HUVEC. Tissue distribution studies and an extended immunohistochemical analysis on the majority of normal human tissues revealed that the Moon-1 molecule displays a unique pattern of expression, being present at high levels on resting and activated vascular endothelium, on the majority of monocytes, platelets, NK cells, and to a lesser extent on T, B, and myeloid cells. The Moon-1 structure of an apparent molecular mass of 120 kDa proved to be a ligand for human CD38, as inferred by the direct binding observed when using a chimeric mouse CD8 alpha-human CD38 (mCD8 alpha-hCD38) molecule as a probe in Western blot experiments. Furthermore, Ab-induced modulation experiments highlighted an association between the Moon-1 molecule and human CD38 on the surface of cell lines coexpressing the two structures, which also share a common regulation system of surface expression. Finally, direct ligation of Moon-1 on T cell lines caused a relevant increase in the cytoplasmic concentration of calcium ([Ca2+]i).
Deaglio
S
S
Department of Genetics, Biology, and Medical Chemistry, University of Torino, Italy.
Dianzani
U
U
Horenstein
A L
AL
Fernández
J E
JE
van Kooten
C
C
Bragardo
M
M
Funaro
A
A
Garbarino
G
G
Di Virgilio
F
F
Banchereau
J
J
Malavasi
F
F
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D001773:Blood Cells / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell; D008198:Lymph Nodes / Q000098:blood supply; D008562:Membrane Glycoproteins; D051379:Mice; D008970:Molecular Weight; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D009928:Organ Specificity; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1