Source:http://linkedlifedata.com/resource/pubmed/id/20888877
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2010-11-15
|
| pubmed:abstractText |
Widely known for its role in adipogenesis and energy metabolism, PPAR? also plays a role in platelet function. To further understand functions of platelet-derived PPAR?, we produced rabbit polyclonal (PoAbs) and mouse monoclonal (MoAbs) antibodies against PPAR? 14mer/19mer peptide-immunogens. Unexpectedly, our work produced two key findings. First, MoAbs but not PoAbs produced against PPAR? peptide-immunogens displayed antigenic crossreactivity with highly conserved PPAR? and PPAR?/?. Similarly, Santa Cruz PoAb sc-7196 was monospecific for PPAR? while MoAb sc-7273 crossreacted with PPAR? and PPAR?/?. Second, immunized rabbits and mice exhibited unusual pathology including cachexia, excessive bleeding, and low platelet counts leading to thrombocytopenia. Spleens from immunized mice were fatty, hemorrhagic and friable. Although passive administration of anti-PPAR? PoAbs failed to induce experimental thrombocytopenia, megakaryocytopoiesis was induced 4-8-fold in mouse spleens. Similarly, marrow megakaryocytopoiesis was enhanced 1.8-4-fold in immunized rabbits. These peptide-immunogens are 100% conserved in human, rabbit and mouse; thus, immune-mediated platelet destruction via crossreactivity with platelet-derived PPAR? likely caused bleeding, thrombocytopenia, and compensatory megakaryocytopoiesis. Such overt pathology would cause significant problems for large-scale production of anti-PPAR? PoAbs. Furthermore, a major pitfall associated with MoAb production against closely related molecules is that monoclonicity does not guarantee monospecificity, an issue worth further scientific scrutiny.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
1873-4863
|
| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2010 Elsevier B.V. All rights reserved.
|
| pubmed:issnType |
Electronic
|
| pubmed:volume |
150
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
417-27
|
| pubmed:dateRevised |
2011-11-1
|
| pubmed:meshHeading |
pubmed-meshheading:20888877-Animals,
pubmed-meshheading:20888877-Antibodies,
pubmed-meshheading:20888877-Antibodies, Monoclonal,
pubmed-meshheading:20888877-Cachexia,
pubmed-meshheading:20888877-Epitope Mapping,
pubmed-meshheading:20888877-Female,
pubmed-meshheading:20888877-Histocytochemistry,
pubmed-meshheading:20888877-Homeostasis,
pubmed-meshheading:20888877-Humans,
pubmed-meshheading:20888877-Intestines,
pubmed-meshheading:20888877-Liver,
pubmed-meshheading:20888877-Mice,
pubmed-meshheading:20888877-Mice, Inbred BALB C,
pubmed-meshheading:20888877-Ovary,
pubmed-meshheading:20888877-PPAR gamma,
pubmed-meshheading:20888877-Peptides,
pubmed-meshheading:20888877-Protein Isoforms,
pubmed-meshheading:20888877-Rabbits,
pubmed-meshheading:20888877-Spleen,
pubmed-meshheading:20888877-Thrombocytopenia,
pubmed-meshheading:20888877-Thrombopoiesis
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
A putative role for platelet-derived PPAR? in vascular homeostasis demonstrated by anti-PPAR? induction of bleeding, thrombocytopenia and compensatory megakaryocytopoiesis.
|
| pubmed:affiliation |
Department of Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, NY 14642, USA. pj simpsonhaidaris@urmc.rochester.edu
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|