CXC chemokines suppress proliferation of myeloid progenitor cells by activation of the CXC chemokine receptor 2

Ximena Sanchez, Katsutoshi Suetomi, Beth Cousins-Hodges, Julie K. Horton, Javier Navarro

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

IL-8 is one of the major mediators of the transendothelial migration of neutrophils from the circulation to the site of injury and infection. In this work we demonstrate that the CXC or α-chemokines, IL-8 and melanoma growth stimulatory activity (MGSA) induce myeloid suppression via direct action on progenitor cells, mediated by activation of the murine homologue of the CXC chemokine receptor-2 (CXCR2) or IL-8R B. We first show that proliferation of the IL-3-dependent murine myeloid progenitor cell line 32D is suppressed by human IL-8 and the functionally and structurally related peptide, MGSA. Second, we show for the first time the high endogenous expression of the murine CXCR2 in 32D cells, as demonstrated by Northern blot analysis, binding to [125I]macrophage inflammatory protein-2, and macrophage inflammatory protein-2-induced calcium responses in 32D cells. Third, we demonstrate that IL-8 and MGSA induce a rise in intracellular calcium in 32D cells. The IL-8- induced Ca2+ response is desensitizing, since a second dose of IL-8 did not trigger a second calcium response. Other chemokines, including neutrophil- activating protein-2, platelet factor-4, RANTES, and macrophage chemotactic protein-1, neither suppressed the proliferation of 32D cells nor induced a rise in intracellular calcium. Finally, the IC50 of IL-8- and MGSA- dependent suppression of proliferation of 32D cells is in good agreement with the EC50 of IL-8- and MGSA-dependent activation of neutrophil Mac-1 up- regulation and chemotaxis. Our studies are consistent with the idea that IL- 8 and MGSA suppress the proliferation of 32D cells by activation of murine CXCR2.

Original languageEnglish (US)
Pages (from-to)906-910
Number of pages5
JournalJournal of Immunology
Volume160
Issue number2
StatePublished - Jan 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sanchez, X., Suetomi, K., Cousins-Hodges, B., Horton, J. K., & Navarro, J. (1998). CXC chemokines suppress proliferation of myeloid progenitor cells by activation of the CXC chemokine receptor 2. Journal of Immunology, 160(2), 906-910.