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.

CONCLUSION:

Plasma HK is a key mediator of acute and chronic inflammatory arthritis in genetically susceptible Lewis rats.

• Authors: Irma M Sainz, Irma Isordia-Salas, Julian L Castaneda, Alexis Agelan, Bo Liu, Raul A DeLa Cadena, Robin A Pixley, Albert Adam, R Balfour Sartor, Robert W Colman
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 52 Issue 8 Pg. 2549-52 (Aug 2005) ISSN: 0004-3591 [Print] United States
• PMID: 16059911 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Drug Combinations
• Kininogen, High-Molecular-Weight
• Peptidoglycan
• Polysaccharides

Topics

• Animals
• Arthritis, Experimental (blood, chemically induced, metabolism, pathology)
• Body Weight
• Drug Combinations
• Foot (pathology)
• Hindlimb
• Injections, Intraperitoneal
• Joints (pathology)
• Kallikrein-Kinin System
• Kininogen, High-Molecular-Weight (deficiency)
• Peptidoglycan (administration & dosage)
• Polysaccharides (administration & dosage)
• Rats
• Rats, Inbred BN
• Rats, Inbred Lew