Ccr5 Blockade Modulates Inflammation and Alloimmunity in Primates.
From: Division of Cardiac Surgery, Department of Surgery, University of Maryland and Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Aug 2007
- ISSN: 0022-1767
- Volume: 179
- Issue: 4
- Pages: 2289-99
- Medium: Print
- Language: English
- Citation (JAMA): Schröder Carsten, Pierson Richard N, Nguyen Bao-Ngoc H, et al. Ccr5 Blockade Modulates Inflammation and Alloimmunity in Primates.. J. Immunol. Aug 2007;179:2289-99
Abstract
Pharmacologic antagonism of CCR5, a chemokine receptor expressed on macrophages and activated T cells, is an effective antiviral therapy in patients with macrophage-tropic HIV infection, but its efficacy in modulating inflammation and immunity is only just beginning to be investigated. In this regard, the recruitment of CCR5-bearing cells into clinical allografts is a hallmark of acute rejection and may anticipate chronic rejection, whereas conventionally immunosuppressed renal transplant patients homozygous for a nonfunctional Delta32 CCR5 receptor rarely exhibit late graft loss. Therefore, we explored the effects of a potent, highly selective CCR5 antagonist, Merck’s compound 167 (CMPD 167), in an established cynomolgus monkey cardiac allograft model. Although perioperative stress responses (fever, diminished activity) and the recruitment of CCR5-bearing leukocytes into the graft were markedly attenuated, anti-CCR5 monotherapy only marginally prolonged allograft survival. In contrast, relative to cyclosporine A monotherapy, CMPD 167 with cyclosporine A delayed alloantibody production, suppressed cardiac allograft vasculopathy, and tended to further prolong graft survival. CCR5 therefore represents an attractive therapeutic target for attenuating postsurgical stress responses and favorably modulating pathogenic alloimmunity in primates, including man.
Mesh Headings (Keywords): Animals, Antibody Formation, Autoimmunity, Cyclosporine, Disease Models, Animal, Graft Survival, HIV Infections, Heart Transplantation, Humans, Immunosuppressive Agents, Inflammation, Isoantibodies, Kidney Transplantation, Macaca fascicularis, Macrophages, Male, Pyrazoles, Receptors, CCR5, Stress, T-Lymphocytes, Transplantation Tolerance, Transplantation, Homologous, Valine, Vascular Diseases
Check for Full Text / PubMed Unique Identifier (PMID): 17675490
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.