Macrophage inflammatory protein-1alpha relates to the recruitment of inflammatory cells in myosin-induced autoimmune myocarditis in rats.
In experimental autoimmune myocarditis (EAM) there is a characteristic initial focal inflammatory response in the myocardium, induced mainly by CD4(+) T cells and macrophages, which leads to massive myocardial damage. Macrophage inflammatory protein-1alpha (MIP-1alpha) induces chemotaxis in lymphocytes, eosinophils, basophils, and macrophages. We assessed the potential role of MIP-1alpha in the pathogenesis of EAM in rats immunized with porcine myosin. Following immunization, the levels of MIP-1alpha mRNA in EAM showed an increase on Day 11 and peaked on Day 17. MIP-1alpha-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-1alpha-positive cells also positive for ED1 (inflammatory macrophages). We then examined the association of MIP-1alpha with the development of myocardial inflammation. Rats were divided into three groups: Group A consisted of EAM rats (n = 10); Group B consisted of EAM rats treated with anti-MIP-1alpha (1 mg/kg) on Days 11, 13, and 15, before the onset of initial inflammation (n = 5); and Group C consisted of EAM rats treated with anti-MIP-1alpha from the start of the initial inflammation on Days 14, 16, and 18 (n = 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 +/- 4%) than in Groups A (51 +/- 6%) or C (50 +/- 6%) (p < 0.01), indicating that the administration of antibody before the initiation of inflammation, in part, will inhibit myocardial inflammation. These data suggest that MIP-1alpha may play an important role in the recruitment of inflammatory cells in the early stages of EAM.
Toyozaki
T
T
Division of Patholog, Chiba University School of Medicine, Chiba, Japan. toyozaki@za2.so-net.ne.jp
Saito
T
T
Shiraishi
H
H
Tsukamoto
Y
Y
Takano
H
H
Nagai
T
T
Hiroshima
K
K
Ohwada
H
H
Ishiyama
S
S
Hiroe
M
M
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017931:DNA Primers; D005260:Female; D019402:Macrophage Inflammatory Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D009205:Myocarditis / Q000378:metabolism / Q000473:pathology*; D009218:Myosins / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017931:DNA Primers; D019402:Macrophage Inflammatory Proteins; D009218:Myosins