Linked Life Data

21703406

Source:http://linkedlifedata.com/resource/pubmed/id/21703406

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-6-27
pubmed:abstractText
Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that is responsible for the survival and proliferation of monocytes and the differentiation of monocytes into macrophages, including Kupffer cells (KCs) in the liver. KCs play an important role in the clearance of several serum enzymes, including aspartate aminotransferase and creatine kinase, that are typically elevated as a result of liver or skeletal muscle injury. We used three distinct animal models to investigate the hypothesis that increases in the levels of serum enzymes can be the result of decreases in KCs in the apparent absence of hepatic or skeletal muscle injury. Specifically, neutralizing M-CSF activity via a novel human monoclonal antibody reduced the CD14(+)CD16(+) monocyte population, depleted KCs, and increased aspartate aminotransferase and creatine kinase serum enzyme levels in cynomolgus macaques. In addition, the treatment of rats with clodronate liposomes depleted KCs and led to increased serum enzyme levels, again without evidence of tissue injury. Finally, in the osteopetrotic (Csf1(op)/Csf1(op)) mice lacking functional M-CSF and having reduced levels of KCs, the levels of serum enzymes are higher than in wild-type littermates. Together, these findings support a mechanism for increases in serum enzyme levels through M-CSF regulation of tissue macrophage homeostasis without concomitant histopathological changes in either the hepatic or skeletal system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1525-2191
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
179
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
240-7
pubmed:meshHeading
pubmed-meshheading:21703406-Animals, pubmed-meshheading:21703406-Antibodies, Monoclonal, pubmed-meshheading:21703406-Antigens, CD14, pubmed-meshheading:21703406-Aspartate Aminotransferases, pubmed-meshheading:21703406-Bone Density Conservation Agents, pubmed-meshheading:21703406-Clodronic Acid, pubmed-meshheading:21703406-Creatine Kinase, pubmed-meshheading:21703406-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21703406-Female, pubmed-meshheading:21703406-Humans, pubmed-meshheading:21703406-Kupffer Cells, pubmed-meshheading:21703406-Liver, pubmed-meshheading:21703406-Macaca fascicularis, pubmed-meshheading:21703406-Macrophage Colony-Stimulating Factor, pubmed-meshheading:21703406-Male, pubmed-meshheading:21703406-Mice, pubmed-meshheading:21703406-Mice, Knockout, pubmed-meshheading:21703406-Monocytes, pubmed-meshheading:21703406-Muscle, Skeletal, pubmed-meshheading:21703406-Osteopetrosis, pubmed-meshheading:21703406-Rats, pubmed-meshheading:21703406-Rats, Sprague-Dawley, pubmed-meshheading:21703406-Receptors, IgG
pubmed:year
2011
pubmed:articleTitle
Increased serum enzyme levels associated with kupffer cell reduction with no signs of hepatic or skeletal muscle injury.
pubmed:affiliation
Department of Biotherapeutics Research & Development, Pfizer Worldwide Research and Development, Cambridge, MA 02140, USA. zaher.radi@pfizer.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't