An anti-CD11d integrin antibody reduces cyclooxygenase-2 expression and protein and DNA oxidation after spinal cord injury in rats.
Our studies have shown that treatment with a monoclonal antibody (mAb) against the CD11d subunit of the leukocyte integrin CD11d/CD18 after spinal cord injury (SCI) decreases intraspinal inflammation, myeloperoxidase activity, lipid peroxidation and protein nitration, improving neurological function in rats. Using severe clip compression SCI in the rat, immunohistochemistry and western blotting were employed to assess the effects of an anti-CD11d mAb treatment on spinal cord cyclooxygenase-2 (COX-2) expression, formation of 8-hydroxy-2-deoxyguanosine (8-OHdG, a marker of RNA and DNA oxidation) and protein carbonylation (a marker of protein oxidation). We also assessed treatment effects on the expression of apurinic/apyrimidinic endonuclease (redox effector factor-1, APE/Ref-1), a multifunctional enzyme involved in the base excision repair of apurinic/apyrimidinic sites in DNA. The expression of COX-2 and formation of 8-OHdG and protein carbonyl groups were increased after SCI while APE/Ref-1 expression was decreased. Anti-CD11d mAb treatment clearly attenuated COX-2 expression and 8-OHdG and protein carbonyl formation and rescued APE/Ref-1 expression after SCI. This study suggests that anti-CD11d mAb treatment significantly reduces intraspinal free radical formation after SCI, thereby reducing protein and DNA oxidative damage. These effects likely underlie tissue preservation and improved neurological function resulting from the mAb treatment.
Laboratory of Spinal Cord Injury, BioTherapeutics Research Group, Robarts Research Institute, London, Ontario, Canada.
Feng
F
Bao
Yuhua
Y
Chen
Gregory A
GA
Dekaban
Lynne C
LC
Weaver
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D051546:Cyclooxygenase 2; D004247:DNA / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D039001:Integrin alpha Chains / Q000276:immunology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D005136:Eye Proteins; D039001:Integrin alpha Chains; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D003849:Deoxyguanosine