Granulocyte macrophage colony stimulating factor (GM-CSF) activity is regulated by a GM-CSF binding molecule in Wallerian degeneration following injury to peripheral nerve axons.
The hematopoietic factor and inflammatory cytokine GM-CSF is involved in PNS and CNS injury and disease, and in macrophage and microglia function regulation. We presently document that injury to PNS axons induces in vivo production of GM-CSF-inhibitor and GM-CSF-augmenter activities. GM-CSF-inhibitor activity was detected in extract and conditioned medium (CM) of injured PNS but not in extract of intact PNS, and was removed from CM by GM-CSF affinity chromatography, suggesting it is carried by a secreted GM-CSF binding molecule. CM further displayed GM-CSF-augmenter activity along with GM-CSF-inhibitor activity but at contrasting concentrations; augmentation at lowest and inhibition at highest. GM-CSF activity is thus regulated during Wallerian degeneration (WD); augmenter activity characterizes the onset and inhibitor activity the later stages of WD.
Mirski
Roni
R
Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School, P.O.B. 12272, Jerusalem 91120, Israel.
Reichert
Fanny
F
Klar
Avihu
A
Rotshenker
Shlomo
S
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D019771:Axotomy; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000032:analysis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016185:Receptors, Interleukin-3 / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology*; D012995:Solubility; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology; D014855:Wallerian Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D021122:Protein Subunits; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016185:Receptors, Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor