Lung Immunogenicity, Rejection, and Obliterative Bronchiolitis

Burke, Conor M.; Glanville, Allan R.; Theodore, James; Robin, Eugene D.

doi:10.1378/chest.92.3.547

Cited by 110 publications

(31 citation statements)

References 11 publications

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“…Similar to the aberrant MHC antigen expression described in rejection of other organs, increased MHC expression on epithelial cells in transplanted lungs is probably responsible for immune rejection resulting in obliterative bronchiolitis [183]. A parallel phenomenon probably occurs during the obstructive airways disease that occurs in relation to graft versus host disease after allogenic bone marrow transplantation [184].…”

Section: Cell-cell Adhesion Moleculesmentioning

confidence: 84%

“…The presence of MHC antigens on epithelial cells is thought to be important for the pathogenesis of airway disease that occurs after lung transplantation [182,183]. Similar to the aberrant MHC antigen expression described in rejection of other organs, increased MHC expression on epithelial cells in transplanted lungs is probably responsible for immune rejection resulting in obliterative bronchiolitis [183].…”

Section: Cell-cell Adhesion Moleculesmentioning

confidence: 99%

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Immunological functions of the pulmonary epithelium

Thompson¹,

Robbins²,

Romberger³

et al. 1995

Eur Respir J

145

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Section: Cell-cell Adhesion Moleculesmentioning

confidence: 84%

Section: Cell-cell Adhesion Moleculesmentioning

confidence: 99%

Immunological functions of the pulmonary epithelium

Thompson¹,

Robbins²,

Romberger³

et al. 1995

Eur Respir J

145

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show abstract

“…The lung is considered one of the most immunogeneic solid organs to be transplanted (35). This most likely has to do with the lung's major role in host defense involving inhaled Ags and pathogens and its large content of mononuclear cells (35).…”

Section: Discussionmentioning

confidence: 99%

Role of CXCL9/CXCR3 Chemokine Biology during Pathogenesis of Acute Lung Allograft Rejection

Belperio

Keane

Burdick

et al. 2003

The Journal of Immunology

113

104

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Acute allograft rejection is a major complication postlung transplantation and is the main risk factor for the development of bronchiolitis obliterans syndrome. Acute rejection is characterized by intragraft infiltration of activated mononuclear cells. The ELR-negative CXC chemokines CXCL9, CXCL10, and CXCL11) are potent chemoattractants for mononuclear cells and act through their shared receptor, CXCR3. Elevated levels of these chemokines in bronchoalveolar lavage fluid have been associated with human acute lung allograft rejection. This led to the hypothesis that the expression of these chemokines during an allogeneic response promotes the recruitment of mononuclear cells, leading to acute lung allograft rejection. We performed studies in a rat orthotopic lung transplantation model of acute rejection, and demonstrated increased expression of CXCL9 and CXCL10 paralleling the recruitment of mononuclear cells and cells expressing CXCR3 to the allograft. However, CXCL9 levels were 15-fold greater than CXCL10 during maximal rejection. Inhibition of CXCL9 decreased intragraft recruitment of mononuclear cells and cellular expression of CXCR3, resulting in lower acute lung allograft rejection scores. Furthermore, the combination of low dose cyclosporin A with anti-CXCL9 therapy had more profound effects on intragraft leukocyte infiltration and in reducing acute allograft rejection scores. This supports the notion that CXCL9 interaction with cells expressing CXCR3 has an important role in the recruitment of mononuclear cells, a pivotal event in the pathogenesis of acute lung allograft rejection.

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“…Keywords: interstitial lung disease; lung allograft rejection; lung transplantation; pleuroparenchymal fibroelastosis; pulmonary fibrosis Increasing evidence suggests that chronic lung allograft dysfunction following lung transplantation is a heterogeneous condition that includes bronchiolitis obliterans syndrome as well as other types of allograft dysfunction. Although bronchiolitis obliterans syndrome, characterized clinically by irreversible obstructive deficits in pulmonary function tests, [1][2][3][4] remains the major cause of late mortality, we recently described a distinct form of chronic lung allograft dysfunction demonstrating restrictive pulmonary function decline, which we designated restrictive allograft syndrome, 5 and which accounts for 25-35% of chronic lung allograft dysfunction. 5,6 Radiologically, a significant proportion of these patients demonstrated an unusual pattern of interstitial fibrosis, often upper lobe-predominant, associated with traction bronchiectasis in computed tomography scans.…”

mentioning

confidence: 99%