Chemokine regulation of hematopoiesis and the involvement of pertussis toxin-sensitive G alpha i proteins.
Chemokines have been implicated in regulation of various aspects of hematopoiesis, including negative regulation of the proliferation of immature subsets of myeloid progenitor cells (MPCs), chemotaxis of MPCs, and survival enhancement of MPCs after delayed growth factor addition. Since chemokine receptors are seven-transmembrane-spanning G-protein-linked receptors and the chemotactic effect in vitro of the CXC chemokine SDF-1 is pertussis toxin (PT)-sensitive, implying the involvement of G alpha i proteins as mediators of SDF-1-induced chemotaxis, we evaluated the effects of PT on other chemokine actions influencing MPCs. While the in vitro survival-enhancing effects of SDF-1 on GM-CSF and steel factor-dependent mouse bone marrow granulocyte macrophage progenitors (CFU-GM) were pertussis toxin-sensitive, the suppressive effects of the CC chemokine MIP-1 alpha and the CXC chemokine IL-8 on colony formation by GM-CSF and steel factor-sensitive CFU-GM were insensitive to pertussis toxin. These results suggest that not all chemokine-mediated effects on MPCs are necessarily mediated through pertussis toxin-sensitive G alpha i proteins.
Broxmeyer
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Departments of Microbiology and Immunology, and Medicine (Hematology/Oncology), the Walther Oncology Center, Indiana University School of Medicine, and the Walther Cancer Institute, Indianapolis, Indiana 46202, USA. hbroxmey@iupui.edu
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Kim
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Hangoc
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Cooper
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Mantel
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D054407:Chemokine CCL4; D054377:Chemokine CXCL12; D018925:Chemokines / Q000494:pharmacology / Q000502:physiology*; D019743:Chemokines, CXC / Q000494:pharmacology / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D003114:Colony-Forming Units Assay; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D016209:Interleukin-8 / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D037342:Pertussis Toxin; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000502:physiology*; D019707:Receptors, Chemokine / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019089:Stem Cell Factor / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D054407:Chemokine CCL4; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D011518:Proto-Oncogene Proteins; D019707:Receptors, Chemokine; D019089:Stem Cell Factor; D010566:Virulence Factors, Bordetella; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D037342:Pertussis Toxin; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498016:Gnai2 protein, mouse