Your browser doesn't support javascript.
loading
Prolyl endopeptidase contributes to early neutrophilic inflammation in acute myocardial transplant rejection.
Payne, Gregory A; Sharma, Nirmal S; Lal, Charitharth V; Song, Chunyan; Guo, Lingling; Margaroli, Camilla; Viera, Liliana; Kumar, Siva; Li, Jindong; Xing, Dongqi; Bosley, Melanie; Xu, Xin; Wells, J Michael; George, James F; Tallaj, Jose; Leesar, Massoud; Blalock, J Edwin; Gaggar, Amit.
Affiliation
  • Payne GA; Division of Cardiovascular Disease, Department of Medicine.
  • Sharma NS; Vascular Biology and Hypertension Program.
  • Lal CV; Comprehensive Cardiovascular Center, and.
  • Song C; Program in Protease and Matrix Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Guo L; Medical Service at Birmingham VA Medical Center, Birmingham, Alabama, USA.
  • Margaroli C; Department of Internal Medicine, University of South Florida, Tampa, Florida, USA.
  • Viera L; Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Kumar S; Program in Protease and Matrix Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Li J; Division of Neonatology, Department of Pediatrics.
  • Xing D; Division of Cardiovascular Disease, Department of Medicine.
  • Bosley M; Department of Surgery.
  • Xu X; Nephrology Research & Training Center, Division of Nephrology, Department of Medicine.
  • Wells JM; Program in Protease and Matrix Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • George JF; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, and.
  • Tallaj J; Program in Protease and Matrix Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Leesar M; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, and.
  • Blalock JE; Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Gaggar A; Department of Internal Medicine, University of South Florida, Tampa, Florida, USA.
JCI Insight ; 6(6)2021 03 22.
Article in En | MEDLINE | ID: mdl-33571164
Altered inflammation and tissue remodeling are cardinal features of cardiovascular disease and cardiac transplant rejection. Neutrophils have increasingly been understood to play a critical role in acute rejection and early allograft failure; however, discrete mechanisms that drive this damage remain poorly understood. Herein, we demonstrate that early acute cardiac rejection increases allograft prolyl endopeptidase (PE) in association with de novo production of the neutrophil proinflammatory matrikine proline-glycine-proline (PGP). In a heterotopic murine heart transplant model, PGP production and PE activity were associated with early neutrophil allograft invasion and allograft failure. Pharmacologic inhibition of PE with Z-Pro-prolinal reduced PGP, attenuated early neutrophil graft invasion, and reduced proinflammatory cytokine expression. Importantly, these changes helped preserve allograft rejection-free survival and function. Notably, within 2 independent patient cohorts, both PGP and PE activity were increased among patients with biopsy-proven rejection. The observed induction of PE and matrikine generation provide a link between neutrophilic inflammation and cardiovascular injury, represent a potential target to reduce allogenic immune responses, and uncover a mechanism of cardiovascular disease that has been previously unrecognized to our knowledge.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Health context: 11_ODS3_cobertura_universal Database: MEDLINE Main subject: Heart Transplantation / Prolyl Oligopeptidases / Graft Rejection / Neutrophils Type of study: Guideline Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Language: En Journal: JCI Insight Year: 2021 Document type: Article

Full text: 1 Collection: 01-internacional Health context: 11_ODS3_cobertura_universal Database: MEDLINE Main subject: Heart Transplantation / Prolyl Oligopeptidases / Graft Rejection / Neutrophils Type of study: Guideline Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Language: En Journal: JCI Insight Year: 2021 Document type: Article