This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Espinola, R. G. Articles by Colman, R. W. Search for Related Content PubMed PubMed Citation Articles by Espinola, R. G. Articles by Colman, R. W.

(American Journal of Pathology. 2004;165:969-976.)
© 2004 American Society for Investigative Pathology

A Monoclonal Antibody to High-Molecular Weight Kininogen Is Therapeutic in a Rodent Model of Reactive Arthritis

Ricardo G. Espinola^*, Audrey Uknis^*, Irma M. Sainz^*, Irma Isordia-Salas^*, Robin Pixley^*, Raul DeLa Cadena^*, Walter Long, Alexis Agelan, John Gaughan, Albert Adam^¶ and Robert W. Colman^*

From The Sol Sherry Thrombosis Research Center^* and the Departments of Medicine, Physiology, and Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania; and the Department of Pharmacy,^¶ University of Montreal, Quebec, Canada

We reported that high-molecular weight kininogen is proangiogenic by releasing bradykinin and that a monoclonal antibody to high-molecular weight kininogen, C11C1, blocked its binding to endothelial cells. We now test if this antibody can prevent arthritis and systemic inflammation in a Lewis rat model. We studied 32 animals for 16 days. Group I (negative control) received saline intraperitoneally. Group II (disease-treated) received peptidoglycan-polysaccharide simultaneously with C11C1. Group III (disease-untreated) received peptidoglycan-polysaccharide simultaneously with isotype-matched mouse IgG. Group IV (disease-free-treated) and group V (disease-free isotype-treated) received saline and C11C1 or mouse IgG. Analysis of joint diameter changes showed a decrease in the C11C1 disease-treated group compared to the disease-untreated group. The hind paw inflammatory score showed a decrease in the intensity and extent of inflammation between the disease-untreated and the C11C1 disease-treated group. Prekallikrein, high-molecular weight kininogen, factor XI, and factor XII were decreased in the disease-untreated group compared to the C11C1 disease-treated group. T-kininogen was increased in the disease-untreated group when compared with the C11C1 disease-treated group. Disease-free groups IV and V did not show any sign of inflammation at any time. This study shows that monoclonal antibody C11C1 attenuates plasma kallikrein-kinin system activation, local and systemic inflammation, indicating therapeutic potential in reactive arthritis.

This article has been cited by other articles:

				L. G. Coffman, J. C. Brown, D. A. Johnson, N. Parthasarathy, R. B. D'Agostino Jr., M. O. Lively, X. Hua, S. L. Tilley, W. Muller-Esterl, M. C. Willingham, et al. Cleavage of high-molecular-weight kininogen by elastase and tryptase is inhibited by ferritin Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L505 - L515. [Abstract] [Full Text] [PDF]

				M. T. Follettie, M. Pinard, J. C. Keith Jr., L. Wang, D. Chelsky, C. Hayward, P. Kearney, P. Thibault, E. Paramithiotis, A. J. Dorner, et al. Organ Messenger Ribonucleic Acid and Plasma Proteome Changes in the Adjuvant-Induced Arthritis Model: Responses to Disease Induction and Therapy with the Estrogen Receptor-{beta} Selective Agonist ERB-041 Endocrinology, February 1, 2006; 147(2): 714 - 723. [Abstract] [Full Text] [PDF]