Linked Life Data

19439197

Source:http://linkedlifedata.com/resource/pubmed/id/19439197

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2009-7-6
pubmed:abstractText
Platelets are reported to be causally involved in experimental hepatitis. Jo2, an agonistic anti-Fas antibody, induces hepatitis in mice. We examined the in vivo behaviors of platelets in mice injected with this antibody (analyzed by measuring 5-hydroxytryptamine, a constituent of platelets). We found that Jo2 induces platelet accumulation predominantly in the liver, and that this hepatic platelet accumulation (HPA) precedes the increases in hepatitis markers (alanine- and asparagine-aminotransferases [ALT and AST]). By electron microscopy, we detected entry of platelets into hepatocytes, and also evidence of apoptosis among hepatocytes. A caspases-3/6/7/8/10 inhibitor prevented the Jo2-induced HPA and hepatitis. In platelet-depleted mice, contrary to our expectations, the Jo2-induced hepatitis was not reduced, and actually the increase in AST was significantly augmented, although the survival time of mice given a lethal dose of Jo2 was significantly increased (nearly doubled). Interestingly, prior induction of HPA by a low dose of lipopolysaccharide markedly reduced Jo2-induced hepatitis. Jo2 also induced HPA and hepatitis in mice deficient in both IL-1 and TNFalpha, although Jo2 increased the blood level of TNFalpha in wild-type mice. These results suggest that in Jo2-induced hepatitis: (i) platelets accumulate predominantly in the liver as a result of hepatic lesions, and that this precedes the release of transaminases from hepatocytes, and (ii) IL-1 and TNFalpha are not essential for Jo2-hepatitis. We hypothesize that platelet accumulation in the liver may, contrary to our expectations, be protective when the hepatitis is local or not severe, but harmful when hepatitis is severe.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1878-1705
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1071-8
pubmed:meshHeading
pubmed-meshheading:19439197-Alanine Transaminase, pubmed-meshheading:19439197-Animals, pubmed-meshheading:19439197-Antibodies, Monoclonal, pubmed-meshheading:19439197-Antigens, CD95, pubmed-meshheading:19439197-Apoptosis, pubmed-meshheading:19439197-Biological Markers, pubmed-meshheading:19439197-Blood Platelets, pubmed-meshheading:19439197-Caspases, pubmed-meshheading:19439197-Cell Movement, pubmed-meshheading:19439197-Drug-Induced Liver Injury, pubmed-meshheading:19439197-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:19439197-Female, pubmed-meshheading:19439197-Interleukin-1alpha, pubmed-meshheading:19439197-Interleukin-1beta, pubmed-meshheading:19439197-Leukocyte Reduction Procedures, pubmed-meshheading:19439197-Lipopolysaccharides, pubmed-meshheading:19439197-Liver, pubmed-meshheading:19439197-Mice, pubmed-meshheading:19439197-Mice, Inbred BALB C, pubmed-meshheading:19439197-Mice, Knockout, pubmed-meshheading:19439197-Microscopy, Electron, pubmed-meshheading:19439197-Tumor Necrosis Factor-alpha
pubmed:year
2009
pubmed:articleTitle
Hepatic platelet accumulation in Fas-mediated hepatitis in mice.
pubmed:affiliation
Department of Oral Molecular Regulation, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't