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, Nora Goren

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Septicemia is an emerging pathological condition involving, among other effects, refractory hypotension and heart dysfunction. Here we have investigated the contribution of resident nonmyocytic cells to heart alterations after lipopolysaccharide administration. These cells contributed to the rapid infiltration of additional inflammatory cells that enhance the onset of heart disease through the release of inflammatory mediators. Early activation of resident monocytic cells played a relevant role on the infiltration process, mainly of major histocompatibility complex class IIand 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, suggesting a significant contribution of nitric oxide and prostanoids to the infiltration process. Under these conditions, the expression of NOS-2 and cylooxygenase-2 in the whole organ was attenuated because cardiomyocytes failed to express these enzymes. However, cardiomyocytes expressed and activated matrix metalloproteinase-9 through mechanisms regulated, at least in part, by nitric oxide and prostaglandins in an additive way. These results directly link the inflammatory response in the heart and extracellular matrix remodeling by the matrix metalloproteinases released by the cardiomyocytes, suggesting that activation and recruitment of inflammatory cells to the heart is a major early event in cardiac dysfunction promoted by septicemia.

Original languageEnglish
Pages (from-to)1567-1576
Number of pages10
JournalAmerican Journal of Pathology
Volume169
Issue number5
DOIs
StatePublished - Nov 2006
Externally publishedYes

Bibliographical note

Funding Information:
Supported by the Ministerio de Educación y Ciencia (grant SAF2005-03022 ), Red CArdioVAscular, Fundacio la Caixa, Fundación Mutua Madrileña, Centro Nacional de Investigaciones Cardiovasculares-Bancaja (fellowship to J.C.).

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