Lung rejectionBronchoalveolar lavage macrophage and lymphocyte phenotypes in lung transplant recipients☆
Section snippets
Methods
BAL samples were taken from 19 clinically well and stable allograft recipients (SLTRs) at routine surveillance. All patients had a forced expiratory volume at 1 second (FEV1) of >90% of best post-operative value at the time of bronchoscopy. SLTRs qualified for inclusion in this study had well-preserved lung function, not only at the time of bronchoscopy but also at 3 months before and 3 months after the time of bronchoscopic assessment (Table I). The same samples were obtained from 5 allograft
Results
BAL differential cell counts are given in Table III. These counts confirmed our previous work,7, 8 and indicated significantly elevated numbers of neutrophils in the SLTRs compared to the normal range, with a clear elevation in neutrophil count in the BOS subjects (p < 0.05 compared with normals, p = 0.08 compared with the stable group). Again, as in our previous work,7, 8 BAL returns were significantly lower in the transplant groups, with the lowest returns in the BOS group (Table III). Our
Discussion
The results of our study confirm our hypothesis that changes in BAL AM and lymphocyte phenotype would be apparent even in stable lung transplant recipients (SLTRs). Our lymphocyte data indicate the presence of an increased number of natural killer (NK) lymphocytes and CD8 suppressor/cytotoxic T cells that expressed increased amounts of the class II MHC marker HLA-DR. More BAL lymphocytes were stained for the cellular adhesion molecules CD11a, CD11b and CD11c, which have been associated with
Acknowledgements
The authors thank Bernadette Orsida for expert technical assistance and sample reception.
References (41)
- et al.
Persistent increases of BAL neutrophils as a predictor of mortality following lung transplant
Chest
(1999) - et al.
Macrophages and allergic lung disease
Immunobiology
(1996) - et al.
Expression of surface markers on alveolar macrophages from symptomatic patients with HIV infection as detected by flow cytometry
Chest
(1994) - et al.
Bronchiolitis obliterans after lung transplantation. A review
Chest
(1998) - et al.
Recognition of a bacterial adhesin by an integrinmacrophage CR3 (αmβ2 Cd11b/CD18) binds filamentous hemagglutinin of Bordetella pertussis
Cell
(1990) - et al.
The in vitro effect of glucocorticoids on phagocytic function of alveolar macrophages
Vet J
(1998) - et al.
Revision of the 1990 working formulation for the classification of pulmonary allograft rejection
J Heart Transplant
(1996) - Novick RJ, Ahmad D, Menkis AH, Reid KR, Pflugfelder PW, McKenzie FN. The importance of acquired diffuse bronchomalacia...
- et al.
The diagnosis of obliterative bronchiolitis after heart–lung and lung transplantationlow yield of transbronchial biopsy
J Heart Lung Transplant
(1993) - et al.
Clinical diagnosis in allograft rejection
Bronchoalveolar lavage neutrophilia is associated with obliterative bronchiolitis after lung transplantationrole of IL-8
J Immunol
Endobronchial biopsy and bronchoalveolar lavage in stable lung transplant recipients and chronic rejection
Am J Respir Crit Care Med
Bronchiolitis obliterans syndrome in lung transplant recipients is associated with increased neutrophil activity and decreased antioxidant status in the lung
Eur Respir J
Inflammatory cells and activation markers in BAL during acute rejection and infection in lung transplant recipientsa prospective, longitudinal study
Eur Respir J
Flow cytometric analysis of lung lymphocytes in lung transplant recipients
Am J Respir Crit Care Med
Pulmonary macrophages
Eur Respir J
Decreased CD11b expression, phagocytosis and oxidative burst in urban particulate pollution exposed human monocytes and alveolar macrophages
J Toxicol Environ Health
The phenotype of alveolar macrophages and its correlation with immune cells in bronchoalveolar lavage
Eur Respir J
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2015, Journal of Clinical VirologyCitation Excerpt :We found that patients developing infections in BAL had significantly lower CD4 T-cell counts than those without infections. BAL specimens have increasingly been used for the diagnosis of infections after lung transplantation and also for the investigation of cell subsets [14,29–31]. Even though BAL provides information on the cellular component present in the alveolar space, the number of lymphocytes comprise a small percentage of total cells making BAL analysis difficult to standardize, thus results regarding the phenotypic analysis of lymphocytes may be contradictory [28,31].
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2012, Journal of Surgical ResearchCitation Excerpt :Such an approach might also lend greater clarity to the role of the macrophage after lung transplantation and explain why proteins that are related to macrophage functionality appear elevated after LARS in our study, such as IFN-γ and IP-10. This is particularly important as the cell profile in obliterative brochiolitis is characterized by a relative decrease in alveolar macrophages and alveolar macrophage surface markers in the setting of increasing neutrophilia and lymphocytosis [22,23] and that pulmonary leukocytes in some with obliterative brochiolitis might even be devoid of inflammatory activity (in other words, “burned out”) [24]. Despite technical advancements and improved immunomodulation strategies, outcomes after lung transplantation remain unfavorable.
Bronchiolitis obliterans syndrome is associated with increased peripheral blood natural killer and natural killer T-like granzymes, perforin, and T-helper-type 1 pro-inflammatory cytokines
2012, Journal of Heart and Lung TransplantationCitation Excerpt :Consistent with this hypothesis, we previously showed that monocytes from the peripheral blood of stable transplant patients produce similar pro-inflammatory cytokines (interleukin [IL]-1, IL-6, IL-12) and increased pro-inflammatory chemokines (IL-8, monocyte chemotactant protein [MCP]-1 and MCP-3) compared with healthy aged-matched controls.11 These pro-inflammatory monocytes enter the lung and form lung macrophages, where they secrete IL-8 attracting neutrophils, (known to be increased in the lungs in BOS)12 and MCP-1/MCP-3 (known chemoattractants for cytotoxic lymphocytes).13 One of the very few studies on NKT-like cells in solid organ transplantation showed an increase in NK cells but no alteration in T or NKT-like cell numbers in patients after heart transplantation, although there was evidence of increased expression of the cytotoxicity effector molecule CD244 on T and NKT-like cells.7
Mycophenolate mofetil reduces alveolar inflammation, acute rejection and graft loss due to bronchiolitis obliterans syndrome after lung transplantation
2010, Pulmonary Pharmacology and TherapeuticsNatural killer cells and transplantation
2010, Natural Killer Cells
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Supported by NHMRC Australia, The Alfred Hospital Foundation, The Alfred Hospital Whole Time Medical Specialist Trust and Glaxo-Wellcome Australia. Dr. Ward is a European Respiratory Society Research Fellow.