Expression of CAP37, a novel inflammatory mediator, in Alzheimer's disease.
Recent evidence suggests that inflammation in the central nervous system plays an important role in the pathogenesis of Alzheimer's disease. However, the identity of the inflammatory mediators, cytokines, and reactive oxygen species, that orchestrate cell death and plaque biogenesis in Alzheimer's disease, have yet to be elucidated. We have identified a novel inflammatory mediator, CAP37 (Cationic Antimicrobial Protein Mi 37 kDa), that promotes mononuclear cell chemotaxis, adhesion of monocytes to endothelium, and release of oxygen radicals from monocytes. In the present immunocytochemical study, we demonstrate the expression of CAP37 in the cerebral microvasculature in Alzheimer's disease. CAP37 was not detected in brain vessels of normal controls or patients with other neuropathologic conditions such as Pick's, Parkinson's, Binswanger's disease, Progressive Supranuclear Palsy, and Candida infection. Treatment of cerebral endothelial cultures with inflammatory mediators, cytokines or beta-amyloid results in the induction of CAP37 expression. These in vitro data showing endothelial-CAP37 expression after beta-amyloid treatment together with the previous demonstration that CAP37 stimulates mononuclear cell migration and activation, suggest that CAP37 could contribute to neuronal injury in Alzheimer's disease.
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
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Pereira
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Kumar
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D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000096:biosynthesis*; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002352:Carrier Proteins; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009410:Nerve Degeneration; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C062991:AZU1 protein, human; D016229:Amyloid beta-Peptides; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D018836:Inflammation Mediators; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha