Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome

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dc.contributor.authorHodge, S.
dc.contributor.authorDean, M.
dc.contributor.authorHodge, G.
dc.contributor.authorHolmes, M.
dc.contributor.authorReynolds, P.
dc.date.issued2011
dc.description.abstract<h4>Background</h4>Mannose binding lectin (MBL) is a key mediator of both innate immunity and efferocytosis (phagocytosis of apoptotic cells) in the airway. Defective efferocytosis results in a net increase in apoptotic material that can undergo secondary necrosis, leading to tissue damage and chronic inflammation. We have shown reduced MBL and efferocytosis in other chronic inflammatory lung diseases; we therefore hypothesized that reduced MBL and efferocytosis in the airways may be a determinant of bronchiolitis obliterans syndrome (BOS) after lung transplantation.<h4>Methods</h4>We investigated MBL (enzyme-linked immunosorbent assay [ELISA]), MBL-mediated complement deposition (UC4, ELISA), and efferocytosis of apoptotic bronchial epithelial cells (flow cytometry) in bronchoalveolar lavage (BAL) and peripheral blood from 75 lung transplant recipients, comprising 16 with stable graft function, 34 stable with proven infection, 25 with BOS, and 14 healthy controls.<h4>Results</h4>In plasma, MBL levels were highly variable (0-17.538 μg/ml), but increased in infected patients vs control (p = 0.09) or stable groups (p = 0.003). There was a similar increase in UC4 in infected patients and a significant correlation between MBL and UC4. There was no correlation between MBL and time after transplant. In BAL, MBL levels were less variable (0-73.3 ng/ml) and significantly reduced in patients with BOS vs controls and stable groups. Efferocytosis was significantly reduced in the BOS group vs control and stable groups (mean [SEM] control, 20% [1.3%]; stable, 20.5% [2.5%]; infected, 17.3% [2.8%]; BOS, 11.3% [1.5%], p = 0.04).<h4>Conclusions</h4>Low levels of MBL in the airway may play a role in reduced efferocytosis, subsequent tissue damage, and BOS after lung transplantation.
dc.description.statementofresponsibilitySandra Hodge, Melinda Dean, Greg Hodge, M Holmes, Paul N Reynolds
dc.identifier.citationJournal of Heart and Lung Transplantation, 2011; 30(5):589-595
dc.identifier.doi10.1016/j.healun.2011.01.710
dc.identifier.issn1053-2498
dc.identifier.issn1557-3117
dc.identifier.orcidHodge, S. [0000-0002-3602-9927] [0000-0002-9401-298X]
dc.identifier.orcidReynolds, P. [0000-0002-2273-1774]
dc.identifier.urihttp://hdl.handle.net/2440/71765
dc.language.isoen
dc.publisherElsevier Science Inc
dc.relation.grantNHMRC
dc.rightsCopyright © 2011 International Society for Heart and Lung Transplantation.
dc.source.urihttps://doi.org/10.1016/j.healun.2011.01.710
dc.subjectLung transplant
dc.subjectBOS
dc.subjectefferocytosis
dc.subjectmacrophage
dc.subjectmannose binding lectin
dc.subjectcomplement
dc.subjectBAL
dc.titleDecreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome
dc.typeJournal article
pubs.publication-statusPublished

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