Infiltration of inflammatory cells plays an important role in matrix metalloproteinase expression and activation in the heart during sepsis

JIMENA CUENCA, PALOMA MARTÍN-SANZ, ALBERTO M. ÁLVAREZ-BARRIENTOS, LISARDO BOSCÁ AND NORA GOREN

AMERICAN JOURNAL OF PATHOLOGY

Lugar: USA; Año: 2006 vol. 169 p. 1567 - 1576

0002-9440

Septicemia is an emerging pathological condition that involves among other effects, refractory hypotension and heart dysfunction. In this work we have investigated the contribution of resident non-myocytic cells to heart alterations after lipopolysaccharide administration. These cells contribute to the rapid infiltration of additional inflammatory cells that enhance the onset of heart disease through the release of inflammatory mediators. Our data show that early activation of resident monocytic cells plays a relevant role on the infiltration process, mainly of MHC class II and CD11b positive cells. This infiltration was significantly impaired in animals lacking the nitric oxide synthase-2 (NOS-2) gene, or after pharmacological inhibition of NOS-2 or cylooxygenase-2 (COX-2), suggesting a significant contribution of NO and prostanoids to the infiltration process. Under these conditions, the expression of NOS-2 and COX-2 in the whole organ was attenuated since cardiomyocytes failed to express these enzymes. However, cardiomyocytes express and activate matrix metalloproteinase-9 (MMPs) through mechanisms regulated, at least in part, by NO and prostaglandins in an additive way. These results provide a direct link between the inflammatory response in the heart and extracellular matrix remodeling by the MMPs released by the cardiomyocytes. These data suggest that the activation and recruitment of inflammatory cells to the heart is a major early event in the cardiac dysfunction promoted by septicemia.