Immunohistochemical expression of cyclooxygenase-2 in normal kidneys.
Cyclooxygenase (COX)-2, the recently described inducible form ofcyclooxygenase, has been shown to be responsible for the inflammatory and tumorigenic effects of prostaglandins; hence the development and expanding clinical use of COX-2 selective inhibitors termed super aspirins. These pharmacologic agents block COX-2 without abrogating the desired physiologic roles of the constitutively expressed isoform COX-1. Therefore, they are now used in place of nonselective COX inhibitors in patients who require prolonged use of nonsteroidal anti-inflammatory agents. However, there are sporadic reports of COX-2-related nephrotoxicity, and the mechanism of this adverse reaction is not known. Also, the pattern of in situ expression of COX-2 in the human kidney is not known. We therefore studied the immunohistochemical expression of COX-2 in normal kidneys obtained from 53 consecutive total nephrectomy specimens. COX-2 immunohistochemistry was performed using affinity purified polyclonal murine antibody and avidin-biotin detection method with citrate antigen retrieval. Also, to localize COX-2 expression to specific cell types, double immunolabeling was performed using avidin-biotin (for COX-2 detection) and alkaline phosphatase (for detection of alpha-smooth muscle actin or factor VIII related antigen). In the cortex, COX-2 was found to be constitutively expressed in the endothelial cells of arteries, arterioles, and glomeruli in all 53 kidneys. COX-2 expression was also found in the cortical thick ascending limb of the loop of Henle (medullary rays and macula densa) in 50 of 53 cases. In the medulla, COX-2 expression was detected in the endothelial lining of the vasa recta in 52 cases and in the collecting ducts in 5 cases. These data show significant constitutive expression of COX-2 in normal kidney and underscore the need for caution in the use of COX-2 selective inhibitors, especially on a long-term basis.
Adegboyega
Patrick A
PA
Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0588, USA. paadegbo@utmb.edu
Ololade
Omiyosoye
O
D000328:Adult; D000368:Aged; D051546:Cyclooxygenase 2; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology*; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases