Neutrophil transendothelial migration potential predicts rejection severity in human cardiac transplantation☆
| Autor: | John M. Fitzpatrick, J McCarthy, Alfred E. Wood, Jim J. Egan, John P. Hurley, David Healy, R. William G. Watson, Conor O'Keane |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Graft Rejection Male Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Neutrophils Biopsy medicine.medical_treatment Lymphocyte Granulocyte Severity of Illness Index Neutrophil Activation Humans Medicine Aged Peroxidase Heart transplantation CD11b Antigen medicine.diagnostic_test biology business.industry General Medicine Middle Aged medicine.disease Transplant rejection Transplantation medicine.anatomical_structure Neutrophil Infiltration Myeloperoxidase Immunology biology.protein Heart Transplantation Female Surgery Cardiology and Cardiovascular Medicine business Infiltration (medical) Immunosuppressive Agents Endocardium |
| Zdroj: | European Journal of Cardio-Thoracic Surgery. 29:760-766 |
| ISSN: | 1010-7940 |
| DOI: | 10.1016/j.ejcts.2006.01.065 |
| Popis: | Objective: Transplant rejection remains a clinical problem despite therapies that focus on lymphocyte suppression, with little attention focused on the neutrophil. Neutrophils are however the first leukocyte to infiltrate the allograft, are capable of causing myocardial damage and may facilitate lymphocytes recruitment. We hypothesised that an early allograft neutrophil infiltration influences rejection severity. Methods: Myocardial neutrophil infiltration was assessed using CD15 and myeloperoxidase immunohistochemistry of rejection surveillance endomyocardial biopsy specimens from human cardiac transplant recipients (n = 18). In patients undergoing cardiac transplantation (n = 10), neutrophils were isolated from multiple perioperative blood samples using a ficoll-based density gradient centrifugation method. The expression of the neutrophil adhesion protein CD11b was then assessed using flow cytometry and compared to subsequent endomyocardial biopsy rejection grades. The effects of contemporary immunosuppressive agents on human neutrophil CD11b were also assessed using healthy control volunteers. Results: Myeloperoxidase staining of endomyocardial biopsies from human heart transplant recipients demonstrated a positive correlation between the degree of neutrophil infiltration and rejection severity at the first postoperative biopsy. Rejection severity was unrelated to ischaemic time. Functionalassessmentof neutrophils obtained fromrecipientswasthen performed.Perioperativetransplantsamplingdemonstrateda significant correlation between the preoperative expression of CD11b and rejection grade at the first postoperative biopsy. In addition, dynamic changes in CD11b expression in the first 24 h positively correlated with subsequent rejection severity. In vitro experiments showed that transplant immunosuppression did not alter neutrophil CD11b expression. Conclusion: This study demonstrates a potentially greater role for neutrophils in cardiac transplantation than previously recognised, and suggests that blockade of the early allograft neutrophil infiltration might prevent subsequent lymphocyte recruitment and attenuate rejection. |
| Databáze: | OpenAIRE |
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