Roles of CD9 molecules in survival and activation of human eosinophils.
CD9 is a cell surface glycoprotein belonging to the transmembrane 4 superfamily. In this report, we demonstrate that cross-linking CD9 with different forms of mAb activates distinct functions of human eosinophils. Anti-CD9 mAb (clone ALB6) immobilized onto tissue culture plates induced eosinophil degranulation. This effect of anti-CD9 mAb (clone ALB6) was unique because other immobilized clones of anti-CD9 mAb (clones FMC56 and ML13) or anti-HLA Class I mAb failed to induce degranulation. In addition, neutrophil degranulation was not provoked by the immobilized clone ALB6, consistent with a lack of expression of CD9 on neutrophils. Eosinophil degranulation induced by anti-CD9 mAb (clone ALB6) was abolished by pretreatment of eosinophils with anti-CD18 mAb, suggesting that beta2 integrins are involved in the reaction. In contrast to the results with immobilized clones, all clones of anti-CD9 mAb in soluble form enhanced eosinophil survival. This enhanced survival was inhibited by anti-granulocyte-macrophage-CSF (GM-CSF) mAb, suggesting that autocrine production of GM-CSF by eosinophils mediated the enhanced survival. In fact, by ELISA and RT-PCR, GM-CSF protein and mRNA were detected in supernatants and cell lysates of eosinophils stimulated by soluble anti-CD9 mAb, but not by immobilized mAb. These results indicate that CD9 serves as a molecule that delivers stimulation signals on eosinophils. The eosinophil's cellular responses may differ and be dependent on the manner of receptor ligation.
Kim
J T
JT
Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Gleich
G J
GJ
Kita
H
H
D015703:Antigens, CD / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D060245:Tetraspanin 29
D015703:Antigens, CD; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; D016178:Granulocyte-Macrophage Colony-Stimulating Factor