Your browser doesn't support javascript.
loading
Pancreatitis-associated ascitic fluid induces hepatocyte death independent of local cytokines.
Murr, Michel M; Yang, Jun; Fier, Adam; Foulis, Philip R; Loughorn, Thomas P; Epling-Burnette, P K; Norman, James G.
Afiliação
  • Murr MM; Department of Surgery, James A. Haley Veterans Hospital, University of South Florida, Tampa 33620, USA.
J Surg Res ; 106(2): 308-13, 2002 Aug.
Article em En | MEDLINE | ID: mdl-12175984
INTRODUCTION: Kupffer-cell-derived cytokines mediate liver injury, yet macrophage pacification does not abolish hepatocyte injury. We undertook this study to examine the role of pancreatitis-associated ascitic fluid (PAAF) in liver injury. METHODS: Pathogen-free PAAF was perfused into healthy rat livers in situ for 60 min (n = 5, sham = 5, LPS = 5). AST, ALT, LDH, and TNF were measured in the effluent. Primary cultures of rat Kupffer cells or hepatocytes were treated with PAAF; AST, ALT, LDH, and TNF were measured and cell proliferation was determined by MTT assay. A hepatocyte human cell line (CCL-13) was treated with PAAF and apoptosis was measured by flow cytometry. RESULTS: Liver perfusion with PAAF induced a >15-fold increase in AST/ALT/LDH (P < 0.001 PAAF vs sham), but not in TNF. In vitro, Kupffer cell viability was sharply reduced by PAAF in a dose-dependent manner; however, 5% PAAF (50% viability) did not induce TNF production from Kupffer cells. PAAF induced a multifold increase in AST/ALT/LDH from fresh hepatocytes (P < 0.001 vs control), which was not attenuated by a protease inhibitor. The CCL-13 cell population was reduced to 15 +/- 2% of baseline by PAAF (P < 0.001 vs control), whereas elastase, trypsin, or TNF had no effect. PAAF increased the percentage of nonviable CCL-13 cells (78 +/- 4% vs 28 +/- 1%, P < 0.001 vs control). Neither protease inhibitor nor heat inactivation of PAAF altered this pattern of hepatocyte death. CONCLUSION: PAAF induces direct hepatocyte injury and death by heat-stable factors other than pancreatic enzymes but not via local production of Kupffer-cell-derived cytokines.
Assuntos
Buscar no Google
Base de dados: MEDLINE Assunto principal: Pancreatite / Líquido Ascítico / Hepatócitos Tipo de estudo: Risk_factors_studies Limite: Animals / Humans / Male Idioma: En Revista: J Surg Res Ano de publicação: 2002 Tipo de documento: Article País de afiliação: Estados Unidos
Buscar no Google
Base de dados: MEDLINE Assunto principal: Pancreatite / Líquido Ascítico / Hepatócitos Tipo de estudo: Risk_factors_studies Limite: Animals / Humans / Male Idioma: En Revista: J Surg Res Ano de publicação: 2002 Tipo de documento: Article País de afiliação: Estados Unidos