Differential effects of human anaphylatoxin C3a on glucose output and flow in rat liver during orthograde and retrograde perfusion : the periportal scavenger cell hypothesis

  • 1) During orthograde perfusion of rat liver human anaphylatoxin C3a caused an increase in glucose and lactate output and reduction of flow. These effects could be enhanced nearly twofold by co-infusion of the carboxypeptidase inhibitor MERGETPA, which reduced inactivation of C3a to C3adesArg. 2) During retrograde perfusion C3a caused a two- to threefold larger increase in glucose and lactate output and reduction of flow than in orthograde perfusions. These actions tended to be slightly enhanced by MERGETPA. 3) The elimination of C3a plus C3adesArg immunoreactivity during a single liver passage was around 67%, irrespective of the perfusion direction and the presence of the carboxypeptidase inhibitor MERGETPA; however, less C3adesArg and more intact C3a appeared in the perfusate in the presence of MERGETPA in orthograde and retrogade perfusions It is concluded that rat liver inactivated human anaphylatoxin C3a by conversion to C3adesArg and moreover eliminated it by an additional process. The inactivation to C3adesArg seemed to be locat1) During orthograde perfusion of rat liver human anaphylatoxin C3a caused an increase in glucose and lactate output and reduction of flow. These effects could be enhanced nearly twofold by co-infusion of the carboxypeptidase inhibitor MERGETPA, which reduced inactivation of C3a to C3adesArg. 2) During retrograde perfusion C3a caused a two- to threefold larger increase in glucose and lactate output and reduction of flow than in orthograde perfusions. These actions tended to be slightly enhanced by MERGETPA. 3) The elimination of C3a plus C3adesArg immunoreactivity during a single liver passage was around 67%, irrespective of the perfusion direction and the presence of the carboxypeptidase inhibitor MERGETPA; however, less C3adesArg and more intact C3a appeared in the perfusate in the presence of MERGETPA in orthograde and retrogade perfusions It is concluded that rat liver inactivated human anaphylatoxin C3a by conversion to C3adesArg and moreover eliminated it by an additional process. The inactivation to C3adesArg seemed to be located predominantly in the proximal periportal region of the liver sinusoid, since C3a was less effective in orthograde perfusions, when C3a first passed the proximal periportal region before reaching the predominant mass of parenchyma as its site of action, than in retrograde perfusions, when it first passed the perivenous area. These data may be evidence for a periportal scavenger mechanism, by which the liver protects itself from systemically released mediators of inflammation that interfere with the local regulation of liver metabolism and hemodynamics.show moreshow less

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Metadaten
Author:Gerhard P. Püschel, Martin Oppermann, Frank Neuschäfer-Rube, Otto Götze, Kurt Jungermann
URN:urn:nbn:de:kobv:517-opus-16747
Series (Serial Number):Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe, ISSN 1866-8372 (paper 040)
Document Type:Postprint
Language:English
Date of Publication (online):2008/03/14
Year of Completion:1991
Publishing Institution:Universität Potsdam
Release Date:2008/03/14
Source:Biochemical and biophysical research communications. - ISSN 0006-291X . - 176 (1991), 3, p. 1218 - 1226
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoKeine Nutzungslizenz vergeben - es gilt das deutsche Urheberrecht
Notes extern:
first published in:
Biochemical and biophysical research communications - 176 (1991), 3 p. 1218 - 1226
ISSN: 0006-291X
doi: 10.1016/0006-291X(91)90415-4