Involvement of Mac-1-Mediated Adherence and Sphingosine 1-Phosphate in Survival of Phorbol Ester-Treated U937 Cells

• Published in: Biochemical and biophysical research communications 1998-03, Vol.244 (3), p.745-750
• Main Authors: Hamada, Koichi, Nakamura, Hitoshi, Oda, Tsukasa, Hirano, Tetsuo, Shimizu, Noriaki, Utiyama, Hiroyasu
• Format: Article
• Language: English
• Subjects: Apoptosis; CD18 Antigens - metabolism; Cell Adhesion; Cell Survival; Humans; Integrins - metabolism; Leukemia; Lysophospholipids; Macrophage-1 Antigen - metabolism; Monocytes - drug effects; Phorbol 12,13-Dibutyrate - pharmacology; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; Tumor Cells, Cultured
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1998.8328

Phorbol esters exert a dual function in human leukemia cells, induction of differentiation and activation of integrin-mediated functions. Here we have shown that the plastic adherence of phorbol ester-treated U937 cells is mediated by expression of integrin Mac-1 (CD11b/CD18) on the cell surface and that these adherent cells exhibit anoikis (apoptosis when adherent cells are detached or adherence is inhibited). We used U937-derived clones overexpressing either antisense RNAs antisense to CD11b and CD18 mRNAs or mRNA from a truncated mutant CD11b gene. We have also shown that apoptosis in non-adherent cells or anoikis was mediated by sphingosine and that survival of adherent cells was achieved by a shift of the dynamic balance between sphingosine and sphingosine 1-phosphate toward the latter by adherence-activated sphingosine 1-kinase.