Potentiation of chemotactic peptide-induced superoxide generation by CD38 ligation in human myeloid cell lines.
CD38 is a type II transmembrane glycoprotein possessing an NAD+ glycohydrolase activity in its extracellular domain. We previously reported that the ligation of CD38 by a monoclonal antibody (mAb), HB-7, induces the tyrosine phosphorylation of cellular proteins including p120(c-cbl) in differentiated human myeloid cell lines and that the phosphorylated p120(c-cbl) is capable of binding to phosphatidylinositol (PI) 3-kinase. In the present study, we found that the agonistic anti-CD38 mAb markedly potentiates superoxide generation stimulated by chemotactic formyl-Met-Leu-Phe receptors in the CD38-producing cells. HB-7 neither generated superoxide by itself nor enhanced the cell response induced by phorbol 12-myristate acetate, indicating that the potentiating action of the anti-CD38 mAb is specific for the stimulation by the GTP-binding protein (G1)-coupled membrane receptors. The potentiation by HB-7 was abolished by prior treatment of the cells with a tyrosine kinase inhibitor, pertussis toxin, or a potent PI 3-kinase inhibitor, wortmannin. HB-7 also enhanced the product formation of PI 3-kinase in response to the chemotactic receptor stimulation, without significant changes in the receptor-stimulated accumulations of inositol-1,4,5-trisphosphate, arachidonate release, and intracellular Ca2+. These results indicate that the CD38-induced tyrosine phosphorylation has a cross-talk with the chemotactic receptor/G1-mediated signal transduction pathway resulting in the enhancement of superoxide generation, probably through the activation of PI 3-kinase.
Tsujimoto
N
N
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku.
Kontani
K
K
Inoue
S
S
Hoshino
S
S
Hazeki
O
O
Malavasi
F
F
Katada
T
T
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000276:immunology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology; D018000:Receptors, Peptide / Q000502:physiology; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D002630:Chemotactic Factors; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D013481:Superoxides; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1