Macrophage Inflammatory Protein-1α Relates to the Recruitment of Inflammatory Cells in Myosin-Induced Autoimmune Myocarditis in Rats

Abstract

SUMMARY:In experimental autoimmune myocarditis (EAM) there is a characteristic initial focal inflammatory response in the myocardium, induced mainly by CD4 ϩ T cells and macrophages, which leads to massive myocardial damage. Macrophage inflammatory protein-1␣ (MIP-1␣) induces chemotaxis in lymphocytes, eosinophils, basophils, and macrophages. We assessed the potential role of MIP-1␣ in the pathogenesis of EAM in rats immunized with porcine myosin. Following immunization, the levels of MIP-1␣ mRNA in EAM showed an increase on Day 11 and peaked on Day 17. MIP-1␣-positive cells were predominantly immunoreactive to OX6 antibody (dendritic cells) and ED2 antibody (resident macrophages) by Day 14. Marked cellular infiltration was seen on Day 17 with the major population of MIP-1␣-positive cells also positive for ED1 (inflammatory macrophages). We then examined the association of MIP-1␣ with the development of myocardial inflammation. Rats were divided into three groups: Group A consisted of EAM rats (n ϭ 10); Group B consisted of EAM rats treated with anti-MIP-1␣ (1 mg/kg) on Days 11, 13, and 15, before the onset of initial inflammation (n ϭ 5); and Group C consisted of EAM rats treated with anti-MIP-1␣ from the start of the initial inflammation on Days 14, 16, and 18 (n ϭ 5). Rats were euthanized on Day 21 and three transverse sections of the heart were prepared to determine the percentage of the area affected by inflammatory lesions. This area of inflammation was significantly smaller in Group B (27 Ϯ 4%) than in Groups A (51 Ϯ 6%) or C (50 Ϯ 6%) (p Ͻ 0.01), indicating that the administration of antibody before the initiation of inflammation, in part, will inhibit myocardial inflammation. These data suggest that MIP-1␣ may play an important role in the recruitment of inflammatory cells in the early stages of EAM. (Lab Invest 2001, 81:929 -936).

Thioredoxin-1 Ameliorates Myosin-Induced Autoimmune Myocarditis by Suppressing Chemokine Expressions and Leukocyte Chemotaxis in Mice

“…[22][23][24]37 In the present study the cardiac expression of MIP-1␣ and MIP-2 was markedly suppressed by rhTRX-1. Our study showed that serum MIP-2 levels in mice with EAM were not significantly different from those of controls, which was inconsistent with previous reports that plasma MIP-2 levels were significantly elevated in CVB3 myocarditisinfected mice on days 7, 10, and 14.…”

Peroxisome Proliferator-Activated Receptor .GAMMA. and Cardiovascular Diseases

“…We previously demonstrated that MIP-1α mRNA and protein are highly expressed in the hearts of rats with EAM from day 11 after first immunization. 57 Th1 cells produce interferon-γ (IFN-γ), which is mainly involved in cell-mediated immune responses, whereas Th2 cells produce IL-4, IL-5, IL-6, IL-10 and IL-13, which participate in humoral responses. Immune dysfunction associated with autoimmune disease is known to involve an imbalance between Th1 and Th2 cells.…”

“…57 The onset of EAM in rats occurs approximately 2 weeks after the first immunization with porcine cardiac myosin. At this time, small numbers of CD4 + T cells and macrophages start to infiltrate into the myocardium and various cytokines are expressed.…”

miR-590-3p Is a Novel MicroRNA in Myocarditis by Targeting Nuclear Factor Kappa-B in vivo

“…Many studies have demonstrated that nuclear factor kappa-B (NF-κB)-induced proinflammation may play an important role in the development of this disease [4,5], during which many proinflammatory cytokines such as interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) are released, and the direct result is necrosis of myocytes. Various immune cells are also recruited to the lesion tissue to amplify the inflammatory reaction during myocarditis [6]. …”