Acute cellular rejection is due in part to an upregulation of chemokine genes, resulting in eventual cell-mediated cytotoxicity. The role of chemokines in acute cardiac allograft rejection is not fully characterized presently. These studies compared the patterns of expression for multiple chemokines in rodent cardiac allograft rejection. Allogeneic transplants were performed from Brown-Norway donors to Lewis recipients. Survival studies utilized daily administration of neutralizing antisera to MCP-1, CINC, and MIP-1alpha. Patterns of mRNA and protein expression were determined by Northern blots and immunohistochemistry. Allogeneic controls rejected at mean of 6.5 days. Neutralization of MCP-1 (10.8 days, P<0.001) and MIP-1alpha (7.5 days, P=0.004) function, but not CINC (6.2 days, P>0.05), significantly prolonged allograft survival. Message expression for the beta chemokines studied were increased by day 2 and continued to increase until day 6 just before rejection, while CINC levels did not change as dramatically after day 2. Chemokine protein levels mirrored mRNA patterns by IHC analysis. MCP-1 and MIP-1alpha appear to play regulatory roles in cardiac allograft rejection, while CINC is expressed, but not functional, in injury development. Beta chemokine activity should be studied further in hope of developing more targeted immunosuppression, or identifying specific chemokines that may be useful for immunosurveillance purposes.
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http://dx.doi.org/10.1016/j.yexmp.2005.01.002 | DOI Listing |
Chin Med J (Engl)
January 2025
Department of Surgery, University of Virginia, Charlottesville, Virginia 22903, USA.
Anal Chim Acta
February 2025
Department of Chemistry, University of Waterloo, Waterloo, ON, Canada. Electronic address:
Background: Normothermic ex situ heart perfusion (ESHP) has emerged as a valid modality for advanced cardiac allograft preservation and conditioning prior to transplantation though myocardial function declines gradually during ESHP thus limiting its potential for expanding the donor pool. Recently, the utilization of dialysis has been shown to preserve myocardial and coronary vasomotor function. Herein, we sought to determine the changes in myocardial metabolism that could support this improvement.
View Article and Find Full Text PDFFront Immunol
January 2025
Section of Immunology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Background: Maintenance immunosuppression is required for suppression of alloimmunity or allograft rejection. However, continuous use of immunosuppressants may lead to various side effects, necessitating the use of alternative immunosuppressive drugs. The early secreted antigenic target of 6 kDa (ESAT-6) is a virulence factor and immunoregulatory protein of mycobacterium tuberculosis (Mtb), which alters host immunity through dually regulating development or activation of various immune cells.
View Article and Find Full Text PDFSci Transl Med
January 2025
Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Long-term, immunosuppression-free allograft survival has been induced in human and nonhuman primate (NHP) kidney recipients after nonmyeloablative conditioning and donor bone marrow transplantation (DBMT), resulting in transient mixed hematopoietic chimerism. However, the same strategy has consistently failed in NHP heart transplant recipients. Here, we investigated whether long-term heart allograft survival could be achieved by cotransplanting kidneys from the same donor.
View Article and Find Full Text PDFTransplantation
November 2024
Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Cardiac allograft vasculopathy (CAV) remains a significant challenge after heart transplantation, necessitating effective surveillance methods. This review centers around the role of coronary computed tomography angiography (CCTA) in CAV surveillance, given its unique capabilities to visualize and quantify CAV in comparison with other imaging modalities, including invasive coronary angiography and intravascular ultrasound. CCTA has shown good diagnostic performance for detecting and monitoring CAV, exemplified by a higher sensitivity and negative predictive value compared with invasive coronary angiography.
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