| Activated neutrophils injure the isolated, perfused rat liver by an oxygen radical-dependent mechanism. | |
| | |
MedLine Citation:
|
PMID: 1951624 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Under certain circumstances, segmented neutrophils (PMNs) injure extrahepatic tissue by releasing toxic oxygen species and degradative enzymes. The authors used an isolated, perfused rat liver preparation to determine whether PMNs might injure the liver. Livers from fasted rats were perfused with Krebs-Ringer bicarbonate buffer (pH 7.4) containing 3% bovine serum albumin (BSA) in a recirculating system. Rat peritoneal PMNs (4 x 10(8] or vehicle (Hank's balanced salt solution [HBSS], pH 7.35) were added, and liver injury was assessed 90 minutes later by release of alanine aminotransferase (ALT) into the perfusion medium and histopathologic analysis of liver sections. Perfusion of livers receiving only HBSS for 90 minutes resulted in a small increase in ALT activity in the perfusion medium but did not significantly alter histologic features of liver sections. Addition of unstimulated PMNs did not increase further the ALT activity and, with the exception of vascular neutrophilia, did not significantly change the histomorphology compared with controls. When PMNs activated with a combination of phorbol myristate acetate (PMA, 31 ng/ml) and lithocholate (100 mumol/l [micromolar]) were added to the perfusion system, however, livers released greater amounts of ALT than those perfused with PMA, lithocholate, and HBSS. Activated PMNs caused a transient reduction in flow of perfusion medium that lasted approximately 5 to 15 minutes. Liver sections had multifocal to coalescing foci of moderate to severe, acute hepatocellular necrosis associated with the areas of intense sinusoidal neutrophilia. In addition a second type of lesion was observed and was characterized by triangular foci of necrosis located adjacent to periportal regions of sinusoids or portal veins containing neutrophilic thrombi. These lesions were void of PMNs and were consistent with infarcts. A combination of superoxide dismutase and catalase added to the perfusion medium (500 U/ml each) prevented the elevation in ALT activity but not the transient reduction in flow. These results indicate that activated PMNs may cause liver injury by an oxygen radical-dependent mechanism. It is unclear whether PMN-derived oxygen radicals, hepatocellular-derived oxygen species resulting from reduced tissue perfusion and reperfusion, or both are involved in the pathogenesis. |
| | |
Authors:
|
L J Dahm; A E Schultze; R A Roth |
Related Documents
:
|
14888824 - The dominant role of the liver in plasma protein synthesis; a direct study of the isola... 7364464 - Effect of glucagon on the perfused rat hind-quarter vessles and on perfused coronary ar... 7752844 - Uptake and distribution of exogenous coq in the mitochondrial fraction of perfused rat ... 9628554 - The effect of photomirex on the in vitro perfused ovary of the rat. 7010714 - A heterophile system in human renal transplantation. viii. the morphological distributi... 11485824 - Pronounced inhibition by a natural anthocyanin, purple corn color, of 2-amino-1-methyl-... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: The American journal of pathology Volume: 139 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 1991 Nov |
Date Detail:
|
Created Date: 1991-12-17 Completed Date: 1991-12-17 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 1009-20 Citation Subset: AIM; IM |
Affiliation:
|
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Alanine Transaminase
/
metabolism Animals Catalase / pharmacology Cell Communication Cells, Cultured Free Radicals Lithocholic Acid / pharmacology Liver / drug effects, metabolism, pathology* Male Neutrophils / drug effects, metabolism, physiology* Oxygen / metabolism, physiology* Perfusion Rats Rats, Inbred Strains Superoxide Dismutase / pharmacology Tetradecanoylphorbol Acetate / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
|
ES04139/ES/NIEHS NIH HHS; ES07146/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Free Radicals; 16561-29-8/Tetradecanoylphorbol Acetate; 434-13-9/Lithocholic Acid; 7782-44-7/Oxygen; EC 1.11.1.6/Catalase; EC 1.15.1.1/Superoxide Dismutase; EC 2.6.1.2/Alanine Transaminase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A survey of occupational therapy curricula.
Next Document: Analysis of T cells and major histocompatibility complex class I and class II mRNA and protein conte...