Abstract 13996: Stabilin-1 is a Marker for Alternative Macrophage Activation in Myocardium of Patients with LVAD Implantation
Macrophages can be activated via the classical and alternative pathway. Classically activated macrophages (M1) are responsible for the initiation of acute inflammatory reactions. Alternatively activated macrophages (M2) regulate resolution of inflammation, healing and tissue remodeling. Not properly exerted M2 functions support chronic inflammation and the development of fibrosis. Stabilin-1 was identified by us as a specific M2 marker. The aim of the current study was to examine alternative macrophage activation by use of stabilin-1 in left ventricular myocardium of patients with dilatative cardiomyopathy and terminal heart failure treated with LVAD implantation. Paraffin sections of myocardium from the site of LVAD implantation at the left ventricular apex from 17 patients were examined for the expression of CD68 and stabilin-1 using immunohistochemistry and double immunofluorescence/confocal microscopy. We identified three different patterns of macrophage distribution and distinct immunophenotypes: 1) in myocardium without evidence of scarring the randomly distributed scattered single macrophages are either negative or positive for stabilin-1 (up to 50% of macrophages were CD68+stabilin-1+); 2) small clusters of 2 to 10 mainly CD68+stabilin-1+ macrophages mostly in paucicellular scars; 3) large clusters of CD68+stabilin-1+ macrophages cellular scars characterized by intensive infiltration of monocytes. Herein stabilin-1 is strongly expressed in clustered macrophages. Moreover, in areas of neovascularization 80% of macrophages were CD68- and strongly stabilin-1+. Our data indicate that 1) alternatively activated macrophages participate in the remodeling process of the myocardium; 2) high expression of stabilin-1 is associated with active localized inflammation and scarring; 3) active localized inflammation influences the repolarization of resting resident macrophages into alternatively activated macrophages; 4) CD68 is not expressed in all macrophages in areas of severe inflammation and neovascularization. Therefore stabilin-1 has to be used in combination with CD68 to validate the number of macrophages as a separate biomarker for the alternative activation of macrophages.
- © 2012 by American Heart Association, Inc.