Enhanced Production of Macrophage Inflammatory Protein 2 (MIP-2) by In Vitro and In Vivo Infections with Encephalomyocarditis Virus and Modulation of Myocarditis with an Antibody against MIP-2

Abstract

Interleukin-8 (IL-8) is a chemotactic cytokine for neutrophils and lymphocytes. Macrophage inflammatory protein 2 (MIP-2) is a murine counterpart of IL-8. The present study was performed to determine whether MIP-2 aggravates murine myocarditis. We examined (i) the MIP-2-producing activity of encephalomyocarditis (EMC) virus-infected cultured macrophages, (ii) serial plasma MIP-2 levels in EMC virus-induced mice by enzyme-linked immunosorbent assay, and (iii) the effects of antimouse MIP-2 monoclonal antibody (MAb) in vivo upon myocarditis. The production of MIP-2 increased in an infection dose-and time-dependent manner in virus-infected RAW 264.7 macrophages. Five-week-old C 3 H/He mice were inoculated with EMC virus. Plasma MIP-2 levels were significantly elevated in mice on days 7 and 14 postinfection. Mice were injected subcutaneously with anti-MIP-2 MAb at 10 g/day (group 2) or 100 g/day (group 3) on days 0 to 5 and were observed until day 21. Uninfected control mice (group 1) were prepared. The survival rate was higher in the anti-MIP-2-treated group (group 3), but not in group 2, than in the control group. Histopathological analysis revealed that cellular infiltration and myocardial necrosis with macrophage and T-cell accumulation were less prominent in the anti-MIP-2 MAb-treated group, but not in group 2, compared to the level in the controls. MIP-2 is an important naturally occurring inflammatory cytokine in myocarditis, and anti-MIP-2 MAb treatment may prevent the inflammatory response.

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.…”

“…19,20 Cook et al 21 reported that MIP-1␣-knockout mice are strongly resistant to coxsackievirus B3 (CVB3)-induced EAM. Kishimoto et al 22,23 also reported that anti-MIP-2 antibody can prevent the inflammatory response in both CVB3-and encephalomyocarditis virus-induced myocarditis. Taken together, MIP-1␣ and MIP-2 are thought to play essential roles in the recruitment of mononuclear effector cells such as macrophages and T lymphocytes, which are critical to the initiation of EAM.…”

Tenascin‐C Aggravates Autoimmune Myocarditis via Dendritic Cell Activation and Th17 Cell Differentiation

“…40–42 As with the cytokines, TN‐C also accelerated the production of chemokines including MCP‐1, MIP‐1α, MIP‐1β, MIP‐2, RANTES, KC, and IP‐10 by DCs (Figure 5B), and they were also increased more in the hearts of WT EAM mice compared to TNKO EAM mice (Figure 4). In previous experimental myocarditis studies, each of MCP‐1, 43 MIP‐1α, 43 MIP‐1β, 44 MIP‐2, 45 RANTES, 44 KC, 46 and IP‐10 47 has been identified as a chemotactic factor effecting the infiltration of various inflammatory cells into inflamed tissue. At the site of injury and inflammation, TN‐C can provide a scaffold for immune cell adhesion and migration.…”

Cardiac mMCP-4+ mast cell expansion and elevation of IL-6, and CCR1/3 and CXCR2 signaling chemokines in an adjuvant-free mouse model of tree nut allergy

“…A recent study using IL-6 knockout mice and IL-6 transgenic mice with selective over expression within the heart tissue reports a key role for IL-6 in myocardial inflammation (Zhang et al 2007). Another previous report in a mouse model of virus induced myocardial inflammation identified CXCL2 as a key player in cardiac inflammation (Kishimoto et al 2001). The chemokine CCL9, an agonist of CCR1 contributes to hypersensitivity reactions (Lean et al 2002).…”