title: Carboxypeptidase N-deficient mice present with polymorphic disease phenotypes on induction of experimental autoimmune encephalomyelitis.
abstract: Carboxypeptidase N (CPN) is a member of the carboxypeptidase family of enzymes that cleave carboxy-terminal lysine and arginine residues from a large number of biologically active peptides and proteins. These enzymes are best known for their roles in modulating the activity of kinins, complement anaphylatoxins and coagulation proteins. Although CPN makes important contributions to acute inflammatory events, little is known about its role in autoimmune disease. In this study we used CPN(-/-) mice in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. Unexpectedly, we observed several EAE disease phenotypes in CPN(-/-) mice compared to wild type mice. The majority of CPN(-/-) mice died within five to seven days after disease induction, before displaying clinical signs of disease. The remaining mice presented with either mild EAE or did not develop EAE. In addition, CPN(-/-) mice injected with complete or incomplete Freund's adjuvant died within the same time frame and in similar numbers as those induced for EAE. Overall, the course of EAE in CPN(-/-) mice was significantly delayed and attenuated compared to wild type mice. Spinal cord histopathology in CPN(-/-) mice revealed meningeal, but not parenchymal leukocyte infiltration, and minimal demyelination. Our results indicate that CPN plays an important role in EAE development and progression and suggests that multiple CPN ligands contribute to the disease phenotypes we observed.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Hu
authors.affiliation: Brown Foundation Institute of Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Rick A
authors.initials: RA
authors.lastname: Wetsel
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Theresa N
authors.initials: TN
authors.lastname: Ramos
authors.affiliation: Brown Foundation Institute of Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Mueller-Ortiz
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Trenton R
authors.initials: TR
authors.lastname: Schoeb
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: sbarnum@uab.edu.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Barnum
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D003711:Demyelinating Diseases / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007962:Leukocytes / Q000276:immunology*; D001121:Lysine Carboxypeptidase / Q000235:genetics / Q000378:metabolism*; D008578:Meninges / Q000473:pathology*; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D013116:Spinal Cord / Q000473:pathology
chemical_list: D001121:Lysine Carboxypeptidase
keywords: CPN; CVF; Carboxypeptidase; Demyelinating disease; EAE; Kinins; MOG; MS/EAE; carboxypeptidase N; cobra venom factor; experimental autoimmune encephalomyelitis; myelin oligodendrocyte glycoprotein
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