Heme oxygenase (HO)-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression.
Heme oxygenase (HO-1, HSP32) catalyzes the oxidation of heme to biliverdin and carbon monoxide, a putative neurotransmitter. In the brain, HO-1 expression has been associated with neuroprotection during oxidative stress and hypoxia. However, consecutive downstream mediation is involved in neoangiogenesis and consequent neoplastic outgrowth. We have analyzed HO-1 expression in 69 oligodendroglioma tissue samples, in rat intracranially transplanted C6 gliomas, and neuropathologically unaltered control brains by immunohistochemistry. Double labeling experiments confirmed the nature of HO-1 expressing cells. Reverse transcription-polymerase chain reaction was used to demonstrate HO-1 gene expression. HO-1 immunoreactivity was predominantly observed in macrophages/microglial cells. The number of HO-1 expressing macrophages/microglial cells was significantly lower in primary oligodendrogliomas than in their matched relapses (P<0.0001) and lower in primary anaplastic oligodendrogliomas than in their relapses (P=0.0006). Prominent accumulation of HO-1 expressing macrophages/microglial cells was observed in perinecrotic areas of both experimental rat and human glioblastoma relapses. HO-1 expressing neurons, macrophages/microglial cells and astrocytes were scattered in areas of infiltrative tumor growth. Surprisingly, HO-1 mRNA was detected in only one glioblastoma multiforme relapse. We conclude from these data that HO-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression in areas of focal necrosis. However, overall biological function of this phenomenon remains to be determined.
Deininger
M H
MH
Institute of Brain Research, University of Tuebingen, Medical School, Calwer Strasse 3, D-72076, Tuebingen, Germany. hirnforschung@uni-tuebingen.de
Meyermann
R
R
Trautmann
K
K
Duffner
F
F
Grote
E H
EH
Wickboldt
J
J
Schluesener
H J
HJ
D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D005909:Glioblastoma / Q000201:enzymology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D017628:Microglia / Q000201:enzymology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009837:Oligodendroglioma / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1