Involvement of interleukin (IL) 8 receptor in negative regulation of myeloid progenitor cells in vivo: Evidence from mice lacking the murine IL-8 receptor homologue

Hal Broxmeyer, Scott Cooper, Grace Cacalano, Nancy L. Hague, Edward Bailish, Mark W. Moore

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Abstract

Expansion of mature neutrophils has been observed in mice lacking the murine interleukin (IL)-8 receptor homolog [mIL-8Rh(-/-)], and human (hu) IL- 8 suppress proliferation of primitive myeloid cells in vitro and in vivo. To evaluate involvement and relevance of murine IL-8 receptor homolog (mIL-8Rh) in negative regulation of myelopoiesis, we studied mIL-8Rh(-/-) and (+/+) mice raised in a normal or germ-free environment. Immature myeloid progenitors from mIL-8Rh(+/+) mice bred under normal or germ-free conditions were significantly suppressed in vitro by recombinant huIL-8, macrophage inflammatory protein (MIP)-1α, platelet factor (PF) 4, interferon inducible protein (IP) 10, monocyte chemotactic peptide (MCP) 1, and H-ferritin. In contrast, progenitors from mIL-8Rh((-/-) mice were insensitive to inhibition by IL-8, but not to these other chemokines and H-ferritin. Mouse MIP-2, a ligand for mIL-8Rh, suppressed progenitors from normal but not mIL-8Rh(-/-) mice. Under normal environmental conditions, enhanced numbers of myeloid progenitors were found in femur, spleen, and blood of mIL-8Rh(-/-) compared with mIL-8Rh(+/+) mice. Numbers of myeloid progenitors were greatly decreased in mIL-8Rh((-/-) and (+/+) mice in germ-free conditions, and were either not significantly enhanced in mIL-8Rh(-/-) mice compared with (+/+) mice or were only moderately so. Differences in progenitors/organ between a germ-free and normal environment were greater for the mIL-8Rh(-/-) mice. These results document selective insensitivity of myeloid progenitor cells from mIL-8Rh(- /-) mice to inhibition by huIL-8 and mouse MIP-2 and a large expansion of myeloid progenitors in these mice, the latter effect being environmentally inducible. This provides strong support for a negative myeloid regulatory role played by the mIL-8Rh in vivo, whose active ligand may be MIP-2.

Original languageEnglish
Pages (from-to)1825-1832
Number of pages8
JournalJournal of Experimental Medicine
Volume184
Issue number5
StatePublished - Nov 1 1996

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Interleukin-8 Receptors
Myeloid Progenitor Cells
Chemokine CXCL2
Apoferritins
Interleukin-8
Chemokine CXCL10
Myelopoiesis
Ligands
Platelet Factor 4
Macrophage Inflammatory Proteins

ASJC Scopus subject areas

  • Immunology

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Involvement of interleukin (IL) 8 receptor in negative regulation of myeloid progenitor cells in vivo : Evidence from mice lacking the murine IL-8 receptor homologue. / Broxmeyer, Hal; Cooper, Scott; Cacalano, Grace; Hague, Nancy L.; Bailish, Edward; Moore, Mark W.

In: Journal of Experimental Medicine, Vol. 184, No. 5, 01.11.1996, p. 1825-1832.

Research output: Contribution to journalArticle

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abstract = "Expansion of mature neutrophils has been observed in mice lacking the murine interleukin (IL)-8 receptor homolog [mIL-8Rh(-/-)], and human (hu) IL- 8 suppress proliferation of primitive myeloid cells in vitro and in vivo. To evaluate involvement and relevance of murine IL-8 receptor homolog (mIL-8Rh) in negative regulation of myelopoiesis, we studied mIL-8Rh(-/-) and (+/+) mice raised in a normal or germ-free environment. Immature myeloid progenitors from mIL-8Rh(+/+) mice bred under normal or germ-free conditions were significantly suppressed in vitro by recombinant huIL-8, macrophage inflammatory protein (MIP)-1α, platelet factor (PF) 4, interferon inducible protein (IP) 10, monocyte chemotactic peptide (MCP) 1, and H-ferritin. In contrast, progenitors from mIL-8Rh((-/-) mice were insensitive to inhibition by IL-8, but not to these other chemokines and H-ferritin. Mouse MIP-2, a ligand for mIL-8Rh, suppressed progenitors from normal but not mIL-8Rh(-/-) mice. Under normal environmental conditions, enhanced numbers of myeloid progenitors were found in femur, spleen, and blood of mIL-8Rh(-/-) compared with mIL-8Rh(+/+) mice. Numbers of myeloid progenitors were greatly decreased in mIL-8Rh((-/-) and (+/+) mice in germ-free conditions, and were either not significantly enhanced in mIL-8Rh(-/-) mice compared with (+/+) mice or were only moderately so. Differences in progenitors/organ between a germ-free and normal environment were greater for the mIL-8Rh(-/-) mice. These results document selective insensitivity of myeloid progenitor cells from mIL-8Rh(- /-) mice to inhibition by huIL-8 and mouse MIP-2 and a large expansion of myeloid progenitors in these mice, the latter effect being environmentally inducible. This provides strong support for a negative myeloid regulatory role played by the mIL-8Rh in vivo, whose active ligand may be MIP-2.",
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