Selective accumulation of cyclooxygenase-1-expressing microglial cells/macrophages in lesions of human focal cerebral ischemia.
Cyclooxygenases (COX; prostaglandin endoperoxide H synthases) are key enzymes in the conversion of arachidonic acid into prostanoids which mediate inflammation, immunomodulation, mitogenesis, ovulation, fewer, apoptosis and blood flow. Here, we report COX-1 expression following focal cerebral infarctions (FCI). In healthy control brains, COX-1 was localized by immunohistochemistry to a few endothelial cells, single neurons and rare, evenly distributed brain microglia/macrophages. In infarctioned brains, COX-1+ cells accumulated highly significantly (P < 0.0001) in peri-infarctional areas and in the developing necrotic core early after infarction. Here, cell numbers remained persistently elevated up to several months post infarction. Further, clusters of COX-1+ cells were located in perivascular regions related to the Virchow-Robin space. Double-labeling experiments confirmed co-expression of COX-1 by CD68+ microglia/macrophages. Co-expression of the activation antigens HLA-DR, -DP, -DQ (MHC class II) or the macrophage inhibitor factor-related protein MRP-8 (S100A8) by most COX-1+ microglia/macrophages was only seen early after infarction. Thus, COX-1 appeared to be expressed in microglial cells regardless of their activation state. However, the prolonged accumulation of COX-1+ microglia/macrophages restricted to peri-infarctional areas enduring the acute post-ischemic inflammatory response points to a role of COX-1 in tissue remodeling or in the pathophysiology of secondary injury. We have identified localized, accumulated COX-1 expression as a potential pharmacological target following FCI. Therefore we suggest that therapeutic approaches based on selective COX-2 blocking might not be sufficient for suppressing the local synthesis of prostanoids.
Schwab
J M
JM
Institute of Brain Research, University of Tübingen, Medical School, Germany. Hirnforschung@uni-tuebingen.de
Nguyen
T D
TD
Postler
E
E
Meyermann
R
R
Schluesener
H J
HJ
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D051545:Cyclooxygenase 1; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D017628:Microglia / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases