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Increased production of vascular endothelial growth factor in peritoneal macrophages of cirrhotic patients with spontaneous bacterial peritonitis

Authors

  • Pilar Cejudo-Martín,

    1. Hormonal Laboratory Hospital Clínic Universitari and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Instituto Reina Sofia de Investigaciones Nefrológicas (IRSIN), University of Barcelona, Barcelona, Spain
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  • Josefa Ros,

    1. Hormonal Laboratory Hospital Clínic Universitari and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Instituto Reina Sofia de Investigaciones Nefrológicas (IRSIN), University of Barcelona, Barcelona, Spain
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  • Miguel Navasa,

    1. Liver Unit-Institut de Malalties Digestives, Hospital Clínic Universitari and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Instituto Reina Sofia de Investigaciones Nefrológicas (IRSIN), University of Barcelona, Barcelona, Spain
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  • Javier Fernández,

    1. Liver Unit-Institut de Malalties Digestives, Hospital Clínic Universitari and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Instituto Reina Sofia de Investigaciones Nefrológicas (IRSIN), University of Barcelona, Barcelona, Spain
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  • Guillermo Fernádez-Varo,

    1. Hormonal Laboratory Hospital Clínic Universitari and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Instituto Reina Sofia de Investigaciones Nefrológicas (IRSIN), University of Barcelona, Barcelona, Spain
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  • Luis Ruiz-del-Arbol,

    1. Gastroenterology Unit, Hospital Ramón y Cajal, Madrid, Spain.
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  • Francisca Rivera,

    1. Hormonal Laboratory Hospital Clínic Universitari and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Instituto Reina Sofia de Investigaciones Nefrológicas (IRSIN), University of Barcelona, Barcelona, Spain
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  • Vicente Arroyo,

    1. Liver Unit-Institut de Malalties Digestives, Hospital Clínic Universitari and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Instituto Reina Sofia de Investigaciones Nefrológicas (IRSIN), University of Barcelona, Barcelona, Spain
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  • Juan Rodés,

    1. Liver Unit-Institut de Malalties Digestives, Hospital Clínic Universitari and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Instituto Reina Sofia de Investigaciones Nefrológicas (IRSIN), University of Barcelona, Barcelona, Spain
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  • Wladimiro Jiménez Ph.D.

    Corresponding author
    1. Hormonal Laboratory Hospital Clínic Universitari and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Instituto Reina Sofia de Investigaciones Nefrológicas (IRSIN), University of Barcelona, Barcelona, Spain
    • Laboratorio Hormonal, Hospital Clínic Universitari, Villarroel 170, Barcelona 08036, Spain
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Abstract

Spontaneous bacterial peritonitis (SBP) is a common complication of cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy. The pathogenesis of these phenomena is poorly known but it has been related to the production of vasoactive cell mediators locally acting on the splanchnic vasculature. Because previous studies showed that peritoneal macrophages of cirrhotic patients may produce high quantities of vascular endothelial growth factor (VEGF), a powerful vessel permeabilizing agent, when stimulated by cytokines and bacterial lipopolysaccharide, the present study was aimed to seek whether peritoneal macrophages of SBP patients are induced to produce increased amounts of VEGF. Our results indicate that the production rate and the messenger RNA (mRNA) and protein expression of this substance are increased in macrophages of patients with SBP in comparison with those of noninfected cirrhotic patients. This characteristic feature is absent in circulating monocytes of these patients. Moreover, enhanced endothelial cell proliferation induced by conditioned medium of macrophages isolated from the ascites of patients with SBP is abolished by anti-VEGF antibody, and peritoneal tissue of cirrhotic patients expresses both VEGF receptors, Flt-1 and KDR. These results, therefore, are consistent with the concept that locally released macrophage-derived VEGF may result in increased vascular permeability and plasma leakage in the peritoneal vessels of cirrhotic patients with SBP. (HEPATOLOGY 2001;34:487-493.)

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