Early Time Course of Immunopathologic Changes in Coronary Arteries of Heterotopically Transplanted Mouse Heart

Lee, Jeong Ryul; Lim, Hong Gook; Suh, Jung Wook

Abstract

BACKGROUND: In this study, we investigated the early time course of expression of the major histocompatibility (MHC) antigens, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 and the histopathological changes in the coronary arteries of cardiac allografts exchanged between inbred mice strains that differ in one loci of class I major histocompatibility antigen (B10.BR to B10.A). MATERIAL AND METHOD: No immunosuppressive therapy was used. Both allografts and the hearts of the recipients were harvested at 7 (group 1, n=6), 15 (group 2, n=6), 21 (group 3, n=6), and 30 (group 4, n=6) days after transplantation. They were examined by immunohistochemistry, microscopy and morphometry. All allografts had contractions at the time of harvest. RESULT: A strong MHC class I antigen expression was present on the endothelial and medial cells of the coronary arteries in group 1 and remained unchanged in the rest of the groups. However, MHC class II reactivity was none or very little at any time. Mild to moderate ICAM-1 expression was observed on the endothelial cells, but not on the medial cells at any time by 30 days. VCAM-1 expression was strong both on the endothelial and medial cells at any time. Moderate degree expression of interleukin-6 was observed from 7 to 30 day specimens. Histopathologically, percentage of affected vessels (vessels with intimal thickening) was less than 10 % in 7 day group and increased up to 50 % at 30 days. Mean percent narrowing of the lumen of the affected vessels revealed less than 20 % at 7 days and 40 % at 30 days. The area occupied by tropomyosin positive cells in the intimal lesion, graded from 0 to 3, showed gradual increase but remained between grade 0 to 1 by 30 days. Medial integrity was also well preserved at any time. Moderate perivascular mononuclear cell infiltration was observed at 7 days and it was progressively increased upto 30 days. Recipients' heart revealed no positive immunopathologic findings.
CONCLUSION
In this study, the early time course of progression of the transplantation vasculopathy was demonstrated in the murine heterotopic heart transplant model.