| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 140, 1451-1461, Copyright © 1992 by American Society for Investigative Pathology
REGULAR ARTICLES |
PL van Lent, LA van den Bersselaar, AE van den Hoek, AA van de Loo and WB van den Berg
Department of Rheumatology, University Hospital St. Radboud, Nijmegen, The Netherlands.
A novel cationic immune-complex-mediated arthritis (ICA) model was developed in mice. The highly cationic protein lysozyme was coupled to poly-L-lysine (PLL) and injected intra-articularly into the knee joint of the mouse, shortly after systemic administration of specific antibodies. A vehement joint inflammation developed, characterized by severe joint swelling and the influx of predominantly polymorphonuclear (PMN) leukocyte. Unique properties were combined in this protein. First, an excellent retention of the antigen in joint structures was found, facilitating sufficient IC formation in the synovial tissue and at the cartilage surface. Secondly, PLL.lysozyme appeared to be a potent inducer of interleukin-1 (IL-1). Similar IL-1 production was measured at 6 hours, in both immune or nonimmune mice. Neutralization with antibodies against either IL-1 alpha or IL-1 beta revealed that IL- 1 alpha was the dominant cytokine. Resident cells were responsible for this IL-1 production since a comparable IL-1 signal was measured after intra-articular injection of PLL.lys in neutropenic mice. We further investigated whether IL-1 and complement factors were involved in the onset of this ICA. Neutralizing the IL-1 production with antibodies directed against IL-1 alpha and beta showed a significant decrease in joint swelling. Complement depletion by cobra venom factor also prevented the onset of arthritis for the greater part. Only a minor swelling remained at 6 hours after eliciting arthritis, which was similar to the swelling after injecting the antigen alone and probably reflects IL-1 mediated inflammation. In this study, the authors show a synergistic action of IL-1 and complement in the onset of cationic ICA. Unique properties of the antigen such as excellent retention and its ability to induce IL-1 are combined within one molecule and make this antigen arthritogenic in the presence of antibodies and complement activation.
This article has been cited by other articles:
 |
|
 |
|
  P L E M van Lent, A B Blom, L Grevers, A Sloetjes, and W B van den Berg Toll-like receptor 4 induced Fc{gamma}R expression potentiates early onset of joint inflammation and cartilage destruction during immune complex arthritis: Toll-like receptor 4 largely regulates Fc{gamma}R expression by interleukin 10 Ann Rheum Dis, March 1, 2007; 66(3): 334 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Schubert, B. Maier, L. Morawietz, V. Krenn, and T. Kamradt Immunization with Glucose-6-Phosphate Isomerase Induces T Cell-Dependent Peripheral Polyarthritis in Genetically Unaltered Mice J. Immunol., April 1, 2004; 172(7): 4503 - 4509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. van Lent, K. C. Nabbe, P. Boross, A. B. Blom, J. Roth, A. Holthuysen, A. Sloetjes, S. Verbeek, and W. van den Berg The Inhibitory Receptor Fc{gamma}RII Reduces Joint Inflammation and Destruction in Experimental Immune Complex-Mediated Arthritides Not Only by Inhibition of Fc{gamma}RI/III but Also by Efficient Clearance and Endocytosis of Immune Complexes Am. J. Pathol., November 1, 2003; 163(5): 1839 - 1848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. J. van de Loo, M. B. Bennink, O. J. Arntz, R. L. Smeets, E. Lubberts, L. A. B. Joosten, P. L. E. M. van Lent, C. J. J. Coenen-de Roo, S. Cuzzocrea, B. H. Segal, et al. Deficiency of NADPH Oxidase Components p47phox and gp91phox Caused Granulomatous Synovitis and Increased Connective Tissue Destruction in Experimental Arthritis Models Am. J. Pathol., October 1, 2003; 163(4): 1525 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Bokarewa and A Tarkowski Local infusion of infliximab for the treatment of acute joint inflammation Ann Rheum Dis, August 1, 2003; 62(8): 783 - 784. [Full Text] [PDF]
|
|
|
|
|
|
A B Blom, P L E M van Lent, A E M Holthuysen, C Jacobs, and W B van den Berg Skewed balance in basal expression and regulation of activating v inhibitory Fc{gamma} receptors in macrophages of collagen induced arthritis sensitive mice Ann Rheum Dis, May 1, 2003; 62(5): 465 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Kaplan, S. K. O'Neill, T. Koreny, M. Czipri, and A. Finnegan Development of Inflammation in Proteoglycan-Induced Arthritis Is Dependent on Fc{gamma}R Regulation of the Cytokine/Chemokine Environment J. Immunol., November 15, 2002; 169(10): 5851 - 5859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.L.E.M. van Lent, R. Licht, H. Dijkman, A.E.M. Holthuysen, J.H.M. Berden, and W.B. van den Berg Uptake of apoptotic leukocytes by synovial lining macrophages inhibits immune complex-mediated arthritis J. Leukoc. Biol., November 1, 2001; 70(5): 708 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Cunnane, A. Madigan, E. Murphy, O. FitzGerald, and B. Bresnihan The effects of treatment with interleukin-1 receptor antagonist on the inflamed synovial membrane in rheumatoid arthritis Rheumatology, January 1, 2001; 40(1): 62 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. K. de Hooge, F. A. J. van de Loo, O. J. Arntz, and W. B. van den Berg Involvement of IL-6, Apart from Its Role in Immunity, in Mediating a Chronic Response during Experimental Arthritis Am. J. Pathol., December 1, 2000; 157(6): 2081 - 2091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. van Meurs, P. van Lent, A. Holthuysen, D. Lambrou, E. Bayne, I. Singer, and W. van den Berg Active Matrix Metalloproteinases Are Present in Cartilage During Immune Complex-Mediated Arthritis: A Pivotal Role for Stromelysin-1 in Cartilage Destruction J. Immunol., November 15, 1999; 163(10): 5633 - 5639. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
