Heart Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Heart Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

Leukocyte integrin Mac-1 promotes acute cardiac allograft rejection.

Shimizu K, Libby P, Shubiki R, Sakuma M, Wang Y, Asano K, Mitchell RN, Simon DI

Donald W. Reynolds Cardiovascular Clinical Research Center, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA. ksmz@rics.bwh.harvard.edu

BACKGROUND: In allograft rejection, recipient leukocytes and alloantibodies first target donor endothelial cells. Although the leukocyte integrin Mac-1 (alpha(Mbeta2), CD11b/CD18) facilitates cell-cell interactions among leukocytes and interactions between leukocytes and endothelial cells or platelets, its role in allograft survival and vasculopathy is incompletely defined. METHODS AND RESULTS: This study examined parenchymal rejection and graft arterial disease after total allomismatched cardiac transplantation (BALB/c donor heart and B6 recipients) in wild-type (WT) and Mac-1-deficient (Mac-1(-/-)) recipients. Recipient Mac-1 deficiency attenuated parenchymal rejection and significantly prolonged cardiac allograft survival from 8.3+/-1.3 days in WT recipient allografts (n=18) to 13.8+/-2.3 days in Mac-1(-/-) recipient allografts (n=6; P<0.0001). Accumulation of neutrophils and macrophages significantly decreased in Mac-1(-/-) compared with WT recipients. Adoptive transfer of WT but not Mac-1(-/-) macrophages to Mac-1(-/-) recipients exacerbated parenchymal rejection and reduced allograft survival; in contrast, adoptive transfer of WT neutrophils did not affect graft survival. Mac-1(-/-) macrophages expressed significantly lower levels of costimulatory molecules both in vivo and in vitro, and mixed lymphocyte reaction using alloantigen-primed Mac-1(-/-) macrophages resulted in significantly lower antigen-presenting function than for WT macrophages. Tumor necrosis factor-alpha production also fell in cultures with Mac-1(-/-) macrophages. Despite attenuation of acute rejection, recipient Mac-1-deficiency did not prevent late graft arterial disease. CONCLUSIONS: These studies demonstrate critical participation of Mac-1 in alloresponses during cellular allograft rejection. These observations establish a molecular target for modulating recipient responses to prolong graft survival.

Published 16 April 2008 in Circulation, 117(15): 1997-2008.
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Articles on Heart Transplant published 15 April 2008:

Infectious, malignant, and autoimmune complications in pediatric heart transplant recipients.   J Pediatr, 152(5): 671-7.

OBJECTIVE: To review clinical courses of pediatric heart transplant survivors after 5 years from transplantation for infections, lymphoproliferative, and autoimmune diseases. STUDY DESIGN: A total of 71 patients were examined in 2 groups, infant recipients (underwent transplant <1 year of age, n = 38) and older recipients (underwent transplant >1 year, n = 33). All patients received comparable immunosuppression. Calculated occurrence rates were reported as means per 10 years of follow-up ... [Abstract] [Full-text]

Articles on Heart Transplant published 31 March 2008:

Extracorporeal membrane oxygenation as a bridge to emergency heart-lung transplantation in a patient with idiopathic pulmonary arterial hypertension.   J Heart Lung Transplant, 27(4): 466-8.

Lung transplantation with or without cardiac transplantation offers the only hope of long-term, symptom-free survival for patients with advanced idiopathic pulmonary arterial hypertension. We describe a patient who underwent an emergency pulmonary embolectomy. During surgery, it was discovered that the patient had idiopathic pulmonary arterial hypertension. After the patient was weaned from cardiopulmonary bypass, pulmonary hypertension caused right-sided heart failure, and a right ventricular ... [Abstract] [Full-text]

Development of a combined heart and carotid artery transplant model to investigate the impact of acute rejection on cardiac allograft vasculopathy.   J Heart Lung Transplant, 27(4): 450-6.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of late allograft loss after heart transplantation. Although clinical studies are suggestive of an association between episodes of acute rejection and subsequent emergence of CAV, direct experimental evidence in support of a causal relationship is lacking. METHODS: We developed a new murine model of CAV in which a carotid artery and a heart graft are simultaneously transplanted into a single recipient. Transplants were ... [Abstract] [Full-text]

Risk factor analysis in pediatric heart transplantation.   J Heart Lung Transplant, 27(4): 408-15.

BACKGROUND: Steady assessment of risk factors will enable identification of patients at higher risk for post-transplant death, and may thus improve organ utilization and outcomes. In this study we aimed to identify the risk factors of mortality in pediatric heart transplantation. METHODS: Between November 1989 and February 2004, there were 116 orthotopic heart transplantations performed in patients <18 years of age at our institution. RESULTS: The 30-day mortality risk was 12% (dilated ... [Abstract] [Full-text]

The effects of pre- and post-transplant anemia on 1-year survival after cardiac transplantation.   J Heart Lung Transplant, 27(4): 394-9.

BACKGROUND: Anemia is associated with a poor prognosis in heart failure. Recent studies have also suggested that anemia may be a predictor of survival after heart transplantation. METHODS: We investigated whether anemia before or after orthotopic cardiac transplantation affected post-transplant survival and analyzed data from a historical cohort of 267 consecutive adult patients who underwent transplantation between 1994 and 1999. Hemoglobin levels immediately before and at 6 weeks after ... [Abstract] [Full-text]

Graft-infiltrating dendritic cells and coronary endothelial dysfunction after human heart transplantation.   J Heart Lung Transplant, 27(4): 387-93.

BACKGROUND: Indirect allorecognition is involved in chronic transplant rejection. We prospectively characterized graft-infiltrating dendritic cells (DCs) in sequential myocardial biopsies (n = 64; 1 to 24 months after transplantation) from 16 patients after heart transplantation (HTx) and analyzed the relation between graft immune activation and structural and functional coronary changes during follow-up. METHODS: DC invasion (immunostaining) in the human myocardium was detectable early after ... [Abstract] [Full-text]

Long-term follow-up of patients eligible, deferred, or ineligible for heart transplantation.   J Heart Lung Transplant, 27(4): 380-6.

BACKGROUND: When a patient is referred to a heart transplantation center, the patient and the physician should know the predicted long-term survival according to the first transplant committee decision. The aim of the study was to describe the follow-up of patients with heart failure referred to a heart transplantation center according to the initial decision to include (eligible), exclude (ineligible), or postpone (deferred) cardiac transplantation. METHODS: The study cohort consisted of 852 ... [Abstract] [Full-text]

Immunohistochemistry staining of C4d to diagnose antibody-mediated rejection in cardiac transplantation.   J Heart Lung Transplant, 27(4): 372-9.

BACKGROUND: Antibody-mediated rejection (AMR) is associated with poorer outcomes in cardiac transplantation. The clinical diagnosis of AMR has been confirmed by immunofluorescence for C4d on fresh-frozen cardiac tissue. Immunohistochemistry (IHC) has been suggested as a more practical diagnostic tool because it can be performed on routine paraffin-embedded tissue. There are few published data about hemodynamics and C4d staining. We prospectively performed C4d staining on endomyocardial biopsies ... [Abstract] [Full-text]

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