Activation of Phosphatidylinositol 3′-Kinase by Insulin-Like Growth Factor-I Rescues Promyeloid Cells from Apoptosis and Permits Their Differentiation into Granulocytes

Qiang Liu, Dan Schacher, Charlotte Hurth, Gregory G. Freund, Robert Dantzer, Keith W. Kelley

Research output: Contribution to journalArticle

Abstract

Insulin-like growth factor-I (IGF-I) promotes cell division and prevents programmed cell death in hemopoietic progenitors. Human HL-60 promyeloid cells differentiate toward the granulocytic lineage when stimulated with retinoic acid (RA) in serum- containing medium. When deprived of serum, however, we found that these cells differentiate poorly in the presence of RA, as assessed by expression of the α subunit of the β2 integrin heterodimer, CD11b/CD18. However, when IGF-I is added to RA-treated cells, the proportion of CD11b-positive cells increases to a level similar to that in RA-treated cells cultured in serum-containing medium. Cells treated with RA alone not only differentiate poorly but also undergo apoptosis, as assessed by flow cytometry using propidium iodide and HO33342. In serum-free medium, one-third of RA-treated cells become apoptotic compared with only 5% apoptotic cells in the absence of RA. However, addition of IGF-I to RA-treated cells prevents the appearance of this apoptotic population and increases phosphatidylinositol 3′-kinase (PI 3-kinase) activity by fivefold. Wortmannin, a PI 3-kinase inhibitor, potently decreases this IGF-I-induced lipid kinase activity, blocks the ability of IGF-I to prevent apoptosis, and inhibits IGF-I-enhanced CD11b expression. These data demonstrate that IGF-I acts on RA-treated progenitors to promote their differentiation along the granulocytic lineage. IGF-I acts by rescuing these cells from apoptotic cell death via a downstream pathway that is dependent upon PI 3-kinase.

Original languageEnglish (US)
Pages (from-to)829-837
Number of pages9
JournalJournal of Immunology
Volume159
Issue number2
StatePublished - Jul 15 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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