title: Modulation of inflammation by kininogen deficiency in a rat model of inflammatory arthritis.
abstract: OBJECTIVE
  To compare inflammatory peripheral arthritis in wild-type and high molecular weight kininogen (HK)-deficient rats, both on the genetically susceptible Lewis background.
  
  
  METHODS
  By backcrossing Brown-Norway HK-deficient rats with Lewis rats for 6 generations, 2 new strains were produced, wild-type F6 and HK-deficient F6, each with a 98.5% Lewis genome. Inflammatory arthritis was induced by intraperitoneal injection of peptidoglycan-polysaccharide (PG-PS), and the clinical, histopathologic, and biochemical responses were compared in both strains.
  
  
  RESULTS
  Eighteen days after PG-PS injection, rats with normal concentrations of HK showed weight loss and marked increase in hind ankle diameter with severe synovial inflammation and cartilage abnormalities. In contrast, HK-deficient rats showed no weight loss (P < 0.05), no increase in hind ankle diameter (P < 0.05), and an absence of inflammatory changes (P < 0.05), as measured by the histologic and morphometric Mankin grading system for synovial and cartilage injury.
  
  
  CONCLUSIONS
  Plasma HK is a key mediator of acute and chronic inflammatory arthritis in genetically susceptible Lewis rats.
authors.affiliation: Temple University, Philadelphia, PA 19140, USA.
authors.forename: Irma M
authors.initials: IM
authors.lastname: Sainz
authors.forename: Irma
authors.initials: I
authors.lastname: Isordia-Salas
authors.forename: Julian L
authors.initials: JL
authors.lastname: Castaneda
authors.forename: Alexis
authors.initials: A
authors.lastname: Agelan
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Raul A
authors.initials: RA
authors.lastname: DeLa Cadena
authors.forename: Robin A
authors.initials: RA
authors.lastname: Pixley
authors.forename: Albert
authors.initials: A
authors.lastname: Adam
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
authors.forename: Robert W
authors.initials: RW
authors.lastname: Colman
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D001835:Body Weight; D004338:Drug Combinations; D005528:Foot / Q000473:pathology; D006614:Hindlimb; D007274:Injections, Intraperitoneal; D007596:Joints / Q000473:pathology; D016234:Kallikrein-Kinin System; D019679:Kininogen, High-Molecular-Weight / Q000172:deficiency*; D010457:Peptidoglycan / Q000008:administration & dosage; D011134:Polysaccharides / Q000008:administration & dosage; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew
chemical_list: D004338:Drug Combinations; D019679:Kininogen, High-Molecular-Weight; D010457:Peptidoglycan; D011134:Polysaccharides