Neutrophil transendothelial migration potential predicts rejection severity in human cardiac transplantation

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 lym...

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Published in:	European journal of cardio-thoracic surgery 2006-05, Vol.29 (5), p.760-766
Main Authors:	Healy, David G., Watson, R. William G., O’Keane, Conor, Egan, Jim J., McCarthy, James F., Hurley, John, Fitzpatrick, John, Wood, Alfred E.
Format:	Article
Language:	eng
Subjects:	Adhesion molecules Adult Aged Biopsy Cardiac CD11b CD11b Antigen - blood CPB = cardiopulmonary bypass Endocardium - enzymology Endocardium - immunology Endocardium - pathology Female Graft Rejection - enzymology Graft Rejection - immunology Heart Transplantation Humans Immunosuppressive Agents - pharmacology ISHLT = International Society for Heart Lung Transplantation Male Middle Aged Neutrophil Neutrophil Activation - immunology Neutrophil Infiltration - drug effects Neutrophils - drug effects Neutrophils - immunology Peroxidase - metabolism Rejection Severity of Illness Index Transplantation
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Summary:	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. Functional assessment of neutrophils obtained from recipients was then performed. Perioperative transplant sampling demonstrated a 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.
ISSN:	1010-7940 1873-734X