Abstract
We have previously described a model of cardiac myosin-induced autoimmune myocarditis in Lewis rats. This autoimmune myocarditis is associated with significant myocardial lymphocytic (CD4+) infiltration and left ventricular dysfunction developing 21 days after initial immunization with myosin. Intercellular Adhesion Molecule-1 (ICAM-1) plays an important role in cell recognition processes such as leukocyte activation and leukocyteendothelial interactions. The role of ICAM-1 in myocarditis is unknown. To determine the relationship of ICAM-1 expression to the development and severity of autoimmune myocarditis, 10 Lewis rats underwent immunization with 1 mg myosin in Complete Freund's Adjuvant on days 1 and 8. As controls, 10 Lewis rats were immunized with Bovine Serum Albumin in Complete Freund's Adjuvant. Control and autoimmune myocarditis rats were sacrificed on days 0, 8, 14, 21 or 28, hearts were removed, frozen, and analyzed by conventional staining with hematoxylin and eosin for histologic grading of the myocarditis and immunohistochemical staining with mouse monoclonal antibodies against rat ICAM-1 and the leukocyte-bound ICAM-1 ligands LFA- α , LFA- β and VLA-4. Specimens were scored in a blinded fashion as 0 (no staining), 1 (mild staining), 2 (moderate staining) or 3 (strong staining) on vascular endothelium and myocardium. Rats immunized with myosin had ICAM-1 expression compared to controls of 1.0 vs. 1.0 on day 8 but 3.0 vs. 1.0 on days 14, 21 and 28. Enhanced expression of LFA- α and LFA- β was noted on days 21 and 28 but not day 14 in rats with myocarditis vs. control rats. No difference in VLA-4 expression was noted in myocarditis rats vs. controls. We conclude that autoimmune myocarditis in rats is associated with significant upregulation of ICAM-1 expression on endothelial cells which pvecedes the development of significant myocardial leUkocytic infiltration. LFA- α and LFA- β expression was enhanced at the time of leukocytic infiltration. The upregulation of ICAM-1 may be involved in the pathophysiology of myocarditis.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.