Lesion-associated expression of transforming growth factor-beta-2 in the rat nervous system: evidence for down-regulating the phagocytic activity of microglia and macrophages.
The mechanisms that control the phagocytic activities of microglia and macrophages during disorders of the nervous system are largely unknown. In the present investigation, we assessed the functional role of transforming growth factor (TGF)beta2 in vitro and studied TGFbeta-2mRNA and protein expression in two CNS lesion paradigms in vivo characterized by fundamental differences in microglia/macrophage behaviour: optic nerve crush exhibiting slow, and focal cerebral ischemia exhibiting rapid phagocytic transformation. Furthermore, we used sciatic nerve crush injury as a PNS lesion paradigm comparable to brain ischemia in its rapid phagocyte response. In normal and degenerating optic nerves, astrocytes strongly and continuously expressed TGF-beta2 immunoreactivity. In contrast, TGF-beta2 was downregulated in Schwann cells of degenerating sciatic nerves, and was not expressed by reactive astrocytes in the vicinity of focal ischemic brain lesions during the acute phagocytic phase. In line with its differential lesion-associated expression pattern, exogenous TGF-beta2 suppressed spontaneous myelin phagocytosis by microglia/macrophages in a mouse ex vivo assay of CNS and PNS Wallerian degeneration. In conclusion, we have identified TGF-beta2 as a nervous system intrinsic cytokine that could account for the differential regulation of phagocytic activities of microglia and macrophages during injury.
Department of Neurology, Julius-Maximilians Universität Würzburg, Germany. stoll_g@klinik.uni-wuerzburg.de
Guido
G
Stoll
Michael
M
Schroeter
Sebastian
S
Jander
Heike
H
Siebert
Anja
A
Wollrath
Christoph
C
Kleinschnitz
Wolfgang
W
Brück
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D020520:Brain Infarction / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D007150:Immunohistochemistry; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D017628:Microglia / Q000502:physiology*; D009409:Nerve Crush; D009420:Nervous System / Q000378:metabolism* / Q000473:pathology; D020221:Optic Nerve Injuries / Q000473:pathology; D010587:Phagocytosis / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053781:Transforming Growth Factor beta2; D014855:Wallerian Degeneration / Q000378:metabolism / Q000473:pathology
D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2