Early anti-inflammatory treatment reduces lipid peroxidation and protein nitration after spinal cord injury in rats.

Abstract

We investigated mechanisms by which a monoclonal antibody (mAb) against the CD11d subunit of the leukocyte integrin CD11d/CD18 improves neurological recovery after spinal cord injury (SCI) in the rat. The effects of an anti-CD11d mAb treatment were assessed on ED-1 expression (estimating macrophage infiltration), myeloperoxidase activity (MPO, approximating neutrophil infiltration), lipid peroxidation, inducible nitric oxide synthase (iNOS) and nitrotyrosine (indicating protein nitration) expression in the spinal cord lesion after severe clip-compression injury. Protein expression was evaluated by western blotting and immunocytochemistry. Lipid peroxidation was assessed by thiobarbituric acid reactive substances (TBARS) production. After anti-CD11d mAb treatment, decreased ED-1 expression at 6-72 h after SCI indicated reduced macrophage infiltration. MPO activity (units/g tissue) was reduced significantly from 114 +/- 11 to 75 +/- 8 (- 34%) at 6 h and from 38 +/- 2 to 22 +/- 4 (- 42%) at 72 h. After SCI, anti-CD11d mAb treatment significantly reduced TBARS from 501 +/- 61 to 296 +/- 17 nm (- 41%) at 6 h and to approximately uninjured values (87 nm) at 72 h. The mAb treatment also attenuated the expression of iNOS and formation of nitrotyrosine at 6-72 h after SCI. These data indicate that anti-CD11d mAb treatment blocks intraspinal neutrophil and macrophage infiltration, reducing the intraspinal concentrations of reactive oxygen and nitrogen species. These effects likely underlie improved tissue preservation and neurological function resulting from the mAb treatment.

• Authors: Feng Bao, Yuhua Chen, Gregory A Dekaban, Lynne C Weaver
• Journal: Journal of neurochemistry (J Neurochem) Vol. 88 Issue 6 Pg. 1335-44 (Mar 2004) ISSN: 0022-3042 [Print] England
• PMID: 15009633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal
• CD11 Antigens
• ITGAD protein, human
• Integrin alpha Chains
• Proteins
• Thiobarbituric Acid Reactive Substances
• 3-nitrotyrosine
• Tyrosine
• Peroxidase
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, rat

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Antibodies, Monoclonal (therapeutic use)
• CD11 Antigens (immunology)
• Cell Movement (drug effects, immunology)
• Disease Models, Animal
• Disease Progression
• Female
• Integrin alpha Chains (antagonists & inhibitors, immunology)
• Lipid Peroxidation (drug effects)
• Macrophages (drug effects, immunology, pathology)
• Neutrophil Infiltration (drug effects, immunology)
• Neutrophils (drug effects, immunology, pathology)
• Nitric Oxide Synthase (drug effects, metabolism)
• Nitric Oxide Synthase Type II
• Peroxidase (metabolism)
• Proteins (metabolism)
• Rats
• Rats, Wistar
• Spinal Cord Injuries (drug therapy, pathology, physiopathology)
• Thiobarbituric Acid Reactive Substances (metabolism)
• Tyrosine (analogs & derivatives, metabolism)