Nature of the Type II Collagen Autoimmunity in Mice Susceptible to Collagen-Induced Arthritis

Holmdahl, Rikard; Andersson, Mikael; Enander, I.; Goldschmidt, Tom; Jansson, Liselotte; Larsson, Per; Mo, John; Nordling, Cecilia; Klareskog, Lars

doi:10.3109/08830188809044770

Cited by 53 publications

(63 citation statements)

References 30 publications

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“…DBA 1 non-MHC genes have a promoting effect on both CIA and prislane-induced arlhritis models [4,8]. The spontaneously developing arlhritis seems to be at least partly controlled by other genes than both CIA and pristane-induced arthritis, since these models are inducibic in many strains which do not develop spontaneous arthrilis [8,19]. Genes determining the strict male sex linkage may provide possibilities lo understand pathogenetic mechanisms in the disease.…”

Section: Discussionmentioning

confidence: 99%

Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice

Holmdahl

Jansson

Andersson

et al. 1992

Clinical and Experimental Immunology

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SUMMARYDBA/1 male mice develop arthritis spontaneously at the age of 4 months. The affected joints show cell-rich pannus rormaliun without T cell infiltration and only limited MHC class II expression. Specific palhogcn-lrce DBA/1 mice from different sources developed ihe same disease. Analyses of inbred mouse strains with various genetic backgrounds and FI hybrids revealed that the disease is genetically dependent of DBA/I recessive genes. However. FI hybrids between DBA/1 and BXSB spontaneously developed arthritis with earlier onset than DBA/I mice, suggesting that the BXSB autoimmune gene background had both permissive and contributing efTects on the development of arthritis. The complete male preponderance for disease susceptibility was investigated by castration and testosterone treatment of DBA/1 males. No arthritis developed after castration and disease susceptibility was restored by testosterone treatment. Arthritis developed only where more than two males were kept in cages, suggesting an influence by aggressive behaviour. Thus, the spontaneous development ofarthritis is dependent on hormonal and behavioural mediated elTects and differs from experimental models for rheumatoid arthritis such as type II collagen-induced arthritis and pristaneinduced arthritis. We conclude that the spontaneously developing arlhritis in the normal DBA/I strain may be more useful as a disease model for osteoarthritis than for rheumatoid arthritis.Keywords spontaneous arthritis type 11 eoilagen testosterone aggressive behaviour

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Section: Discussionmentioning

confidence: 99%

Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice

Holmdahl

Jansson

Andersson

et al. 1992

Clinical and Experimental Immunology

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“…Female DBA/1 (H-2 q ) mice (5 weeks old; purchased from Japan SLC, Shizuoka, Japan) and Lewis rats (8-10 weeks old; Japan SLC) were housed in the pathogen-free facility of the Animal Resource Center, Kagoshima University. To generate arthritis models, mice and rats were immunized with bovine type II collagen plus Freund's complete and incomplete adjuvant (Chondrex, Redmond, WA), respectively (6,17). Collageninduced arthritis (CIA) generally developed 2-3 weeks after the second immunization.…”

Section: Methodsmentioning

confidence: 99%

Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis

Hamada¹,

Torikai²,

Kuwazuru³

et al. 2008

Arthritis & Rheumatism

106

111

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Objective. Tissue hypoxia is closely associated with arthritis pathogenesis, and extracellular high mobility group box chromosomal protein 1 (HMGB-1) released from injured cells also has a role in arthritis development. This study was thus undertaken to investigate the hypothesis that extracellular HMGB-1 may be a coupling factor between hypoxia and inflammation in arthritis.Methods. Concentrations of tumor necrosis factor ␣, interleukin-6, vascular endothelial growth factor, lactic acid, lactate dehydrogenase, and HMGB-1 were measured in synovial fluid (SF) samples from patients with inflammatory arthropathy (rheumatoid arthritis and pseudogout) and patients with noninflammatory arthropathy (osteoarthritis). The localization of tissue hypoxia and HMGB-1 was also examined in animal models of collagen-induced arthritis (CIA). In cellbased experiments, the effects of hypoxia on HMGB-1 release and its associated cellular events (i.e., protein distribution and cell viability) were studied.Results. In SF samples from patients with HMGB-1-associated inflammatory arthropathy (i.e., samples with HMGB-1 levels >2 SD above the mean level in samples from patients with noninflammatory arthropathy), concentrations of HMGB-1 were significantly correlated with those of lactic acid, a marker of tissue hypoxia. In CIA models in which the pathologic phenotype could be attenuated by HMGB-1 neutralization, colocalization of HMGB-1 with tissue hypoxia in arthritis lesions was also observed. In cell-based experiments, hypoxia induced significantly increased levels of extracellular HMGB-1 by the cellular processes of secretion and/or apoptosis-associated release, which was much more prominent than the protein release in necrotic cell injury potentiated by oxidative stress.Conclusion. These findings indicate that tissue hypoxia and its resultant extracellular HMGB-1 might play an important role in the development of arthritis.High mobility group box chromosomal protein 1 (HMGB-1) is a nuclear architectural protein that is released from necrotic cells (1) and/or secreted from activated macrophages (2,3). It has been identified as a mediator of endotoxin-induced lethality (2,4) and a causative factor in arthritis (3,5-7), acting, at least in part, as a proinflammatory cytokine (1-11). Engagement of the receptor for advanced glycation end products (RAGE) by extracellular HMGB-1 triggers activation of proinflammatory signaling pathways (10,11), such as those resulting in elaboration of reactive oxygen inter-

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“…The severity of arthritis after the triggering immunization corresponded with the serum level of B-CIIrecognizing antibodies of the IgM isotype. Holmdahl et a1 (22) provided evidence that the isotype of the anti-CII antibodies in mice immunized with native CII is governed by class I1 MHC antigens (H-2q). This could also be the case in our outbred population of rhesus monkeys.…”

Section: Wfmentioning

confidence: 99%

Collagen‐induced arthritis in an outbred group of rhesus monkeys comprising responder and nonresponder animals. Relationship between the course of arthritis and collagen‐specific immunity

et al. 1991

Arthritis & Rheumatism

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It is speculated that the autoimmune response to type II collagen (CII) is a driving force in the pathogenesis of human rheumatoid arthritis (RA). In this report, we describe the relationship between the induction of collagen arthritis and the CII‐specific humoral, as well as cellular, immune response in rhesus monkeys. Ten of 14 monkeys immunized with bovine type II collagen (B‐CII) developed polyarthritis. Susceptible animals showed a T cell response to B‐CII; resistant animals did not. After the primary immunization, the humoral response to B‐CII, as well as to rhesus monkey type II collagen, was dominated by antibodies of the IgM isotype in the susceptible animals and by antibodies of the IgG isotype in the resistant animals. Because of the close phylogenic relationship between the rhesus monkey and humans, these data contribute valuable information about the role of CII‐specific immunity in the pathogenesis of human RA.

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Nature of the Type II Collagen Autoimmunity in Mice Susceptible to Collagen-Induced Arthritis

Cited by 53 publications

References 30 publications

Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice

Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice

Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis

Collagen‐induced arthritis in an outbred group of rhesus monkeys comprising responder and nonresponder animals. Relationship between the course of arthritis and collagen‐specific immunity

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