Inflammation and ischemia: Macrophages activated by fibronectin fragments enhance the survival of injured cardiac myocytes

JoAnn Trial, Roger D. Rossen, Jose Rubio, Anne A Knowlton

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Proteolytic enzymes, released early in the course of an inflammatory response, hydrolyze fibronectin, producing fragments of the parent molecule that alter monocyte phenotype and migratory behavior. Here we test the hypothesis that macrophages, stimulated by the dominant 110-120 kd fibronectin fragments (FNf), as are found in lymphatic fluid draining sites of cardiac ischemia-reperfusion injury, produce factors that promote the survival of injured parenchymal cells. Rat splenic macrophages stimulated in vitro with purified FNf produced soluble factors that protected hypoxic rat cardiac myocytes from death by apoptosis. Addition of blocking antibodies specific for tumor necrosis factor-α (TNF-α), fibroblast growth factor-1 (FGF-1), insulin-like growth factor I (IGF-I), and leukemia inhibitory factor (LIF) partly reduced the protection against apoptosis provided to hypoxic cardiac myocytes by cell-free culture supernatants from FNf-stimulated macrophages. Complete blockade of this protection was achieved by a combination of antibodies specific for FGF-1, IGF-I, and LIF. Stimulation of human monocyte-derived macrophages in vitro with FNf significantly increased their output of TNF-α, FGF-1, IGF-I, and LIF. These results suggest that tissue degradation products, released in the early hours of an inflammatory response, stimulate tissue-infiltrating macrophages to protect injured but still viable parenchymal cells from death by apoptosis.

Original languageEnglish (US)
Pages (from-to)538-545
Number of pages8
JournalExperimental Biology and Medicine
Volume229
Issue number6
StatePublished - Jun 2004
Externally publishedYes

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Keywords

  • Apoptosis
  • Cytokines
  • Fibronectin
  • Ischemia
  • Monocytes/macrophages

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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