LPS promotes CB3-induced myocarditis in resistant B10.A mice

Lane, James R.; Neumann, David; Lafond-Walker, Anne; Herskowitz, Ahvie; Rose, Noel R.

doi:10.1016/0008-8749(91)90396-s

Cited by 68 publications

(37 citation statements)

References 24 publications

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“…We are currently varying our immunization regimen to test whether the additional stimulus provided by live infection can be afforded by addition of immune stimulants such as interleukin-1, tumor necrosis factor alpha, and lipopolysaccharide. It is notable that inclusion of each of these with coxsackieviral infection of normally resistant mice promoted cardiac inflammation (19,20).…”

Section: Discussionmentioning

confidence: 99%

A Cardiac Myosin-Specific Autoimmune Response Is Induced by Immunization withTrypanosoma cruziProteins

et al. 2004

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Trypanosoma cruzi is the protozoan parasite that causes Chagas' heart disease, a potentially fatal cardiomyopathy prevalent in Central and South America. Infection with T. cruzi induces cardiac myosin autoimmunity in susceptible humans and mice, and this autoimmunity has been suggested to contribute to cardiac inflammation. To address how T. cruzi induces cardiac myosin autoimmunity, we investigated whether immunity to T. cruzi antigens could induce cardiac myosin-specific autoimmunity in the absence of live parasites. We immunized A/J mice with a T. cruzi Brazil-derived protein extract emulsified in complete Freund's adjuvant and found that these mice developed cardiac myosin-specific delayed-type hypersensitivity (DTH) and autoantibodies in the absence of detectable cardiac damage. The induction of autoimmunity was specific since immunization with extracts of the related protozoan parasite Leishmania amazonensis did not induce myosin autoimmunity. The immunogenetic makeup of the host was important for this response, since C57BL/6 mice did not develop cardiac myosin DTH upon immunization with T. cruzi extract. Perhaps more interesting, mice immunized with cardiac myosin developed T. cruzi-specific DTH and antibodies. This DTH was also antigen specific, since immunization with skeletal myosin and myoglobin did not induce T. cruzi-specific immunity. These results suggest that immunization with cardiac myosin or T. cruzi antigen can induce specific, bidirectionally cross-reactive immune responses in the absence of detectable cardiac damage.Trypanosoma cruzi is the protozoan parasite that causes Chagas' heart disease (CHD), a potentially fatal cardiomyopathy resulting in dilated tissue. Approximately 16 million people are infected with this protozoan parasite, and 120 million are at risk of infection in Central and South America (28). CHD develops in roughly one-third of T. cruzi-infected individuals as an acute or chronic myocarditis of variable degree (reviewed in reference 39). Among the various mechanisms invoked to explain the pathogenesis of CHD, autoimmunity is one that both has been supported by much experimental evidence and has received much criticism. There is no doubt that autoimmunity results from chronic T. cruzi infection of humans and experimental animals. The questions are (i) whether this autoimmunity is pathogenic and (ii) by what mechanism(s) autoimmunity is induced. The debate surrounding this issue is long-standing (reviewed in references 17, 22, 39, and 40).T. cruzi infection induces humoral and cellular autoimmunity to a diverse set of autoantigens (reviewed in references 17 and 22), including cardiac myosin. Myosin-specific autoimmunity is induced in both humans (8) and experimental models (24) upon T. cruzi infection. In previous work (24), it was found that within weeks of infection, A/J mice acutely infected with T. cruzi developed severe myocarditis accompanied by myosinspecific delayed-type hypersensitivity (DTH) and antibody production. Autoimmunity to cardiac myosin has also been rep...

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Section: Discussionmentioning

confidence: 99%

A Cardiac Myosin-Specific Autoimmune Response Is Induced by Immunization withTrypanosoma cruziProteins

et al. 2004

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“…6) and Coxsackie virus B3 (52). The myocarditis generated from Coxsackie virus B3 infection is associated with macrophage accumulation so the blunted myocardial inflammation in the R␤1 Ϫ/Ϫ mice likely reflects decreased macrophage accumulation (53,54).…”

Section: Discussionmentioning

confidence: 99%

IL-12 p40 Homodimer-Dependent Macrophage Chemotaxis and Respiratory Viral Inflammation Are Mediated through IL-12 Receptor β1

Russell

Yan

Fan

et al. 2003

The Journal of Immunology

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Leukocyte recruitment to the airway lumen is a central feature of inflammatory conditions such as asthma and respiratory viral infection. Characterization of mediators that regulate leukocyte recruitment in these conditions revealed increased IL-12 p40 homodimer (p80) levels were associated with enhanced airway macrophage accumulation. To examine this association, we used in vivo and in vitro assays to demonstrate p80, but not IL-12 or p40, provided a macrophage chemoattractant signal. Macrophages from genetically deficient mice indicated p80-dependent chemotaxis was independent of IL-12 and required IL-12Rβ1 (Rβ1) expression. Furthermore, analysis of murine cell lines and primary culture macrophages revealed Rβ1 expression, with an intact cytoplasmic tail, was necessary and sufficient to mediate p80-dependent chemotaxis. To examine the role for Rβ1 in mediating macrophage accumulation in vivo, we contrasted Sendai virus-driven airway inflammation in wild-type and Rβ1-deficient mice. Despite similar viral burden and production of the macrophage chemoattractant p80, the Rβ1-deficient mice displayed a selective decrease in airway macrophage accumulation and resistance to viral-dependent mortality. Thus, Rβ1 mediates p80-dependent macrophage chemotaxis and inhibition of the p80-Rβ1 interaction may provide a novel anti-inflammatory strategy to manipulate the inflammation associated with asthma and respiratory viral infection.

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“…In addition to T cell repertoire recognition of myocarditic epitopes, other factors such as activation of APCs and the local production of cytokines may influence and perpetuate autoimmune reactivity in vivo (18,21,45,46). Normal heart may not be susceptible to autoreactive T cell attack unless interstitial APCs of myocardium are activated and up-regulate their surface MHC class II expression, which is mediated through the cytokines such as IFN-␥ and TNF-␣ (46 -49).…”

Section: Figurementioning

confidence: 99%

Cryptic Epitope Identified in Rat and Human Cardiac Myosin S2 Region Induces Myocarditis in the Lewis Rat

Heuser

Kosanke

et al. 2004

The Journal of Immunology

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Myocarditis is a common cause of dilated cardiomyopathy leading to heart failure. Chronic stages of myocarditis may be initiated by autoimmune responses to exposed cardiac Ags after myocyte damage. Cardiac myosin, a heart autoantigen, induced experimental autoimmune myocarditis (EAM) in susceptible animals. Although cardiac myosin-induced myocarditis has been reported in Lewis rats, the main pathogenic epitope has not been identified. Using overlapping synthetic peptides of the S2 region of human cardiac myosin, we identified an amino acid sequence, S2–16 (residues 1052–1076), that induced severe myocarditis in Lewis rats. The myocarditic epitope was localized to a truncated S2–16 peptide (residues 1052–1073), which contained a sequence identical in human and rat cardiac myosin. The S2–16 peptide was not myocarditic for three other strains of rats, in which the lack of myocarditis was accompanied by the absence of strong S2–16-specific lymphocyte responses in vitro. For Lewis rats, S2–16 was characterized as a cryptic epitope of cardiac myosin because it did not recall lymphocyte and Ab responses after immunization with cardiac myosin. Lymphocytes from S2–16 immunized rats recognized not only S2–16, but also peptides in the S2–28 region. Furthermore, peptide S2–28 was the dominant epitope recognized by T cells from cardiac myosin immunized rats. S2–16 was presented by Lewis rat MHC class II molecules, and myocarditis induction was associated with an up-regulation of inflammatory cytokine production. S2–16-induced EAM provides a defined animal model to investigate mechanisms of EAM and modulation of immune responses to prevent autoimmune myocarditis.

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LPS promotes CB3-induced myocarditis in resistant B10.A mice

Cited by 68 publications

References 24 publications

A Cardiac Myosin-Specific Autoimmune Response Is Induced by Immunization withTrypanosoma cruziProteins

A Cardiac Myosin-Specific Autoimmune Response Is Induced by Immunization withTrypanosoma cruziProteins

IL-12 p40 Homodimer-Dependent Macrophage Chemotaxis and Respiratory Viral Inflammation Are Mediated through IL-12 Receptor β1

Cryptic Epitope Identified in Rat and Human Cardiac Myosin S2 Region Induces Myocarditis in the Lewis Rat

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