BACKGROUND: Prostaglandin E(2) (PGE(2)) is thought to play a role in the pathogenesis of aspirin-sensitive asthma (ASA). OBJECTIVE: We sought to extend our previous observations implicating impaired inflammatory cell responsiveness to PGE(2) as a pathogenetic mechanism in patients with aspirin-sensitive rhinosinusitis to the bronchial mucosa in patients with ASA. METHODS: Immunohistochemistry was used to enumerate inflammatory cells and their expression of cysteinyl leukotriene receptors 1 and 2 (CysLT(1) and CysLT(2)) and the PGE(2) receptors E-prostanoid 1 to 4 (EP(1)-EP(4)) in bronchial biopsy specimens from patients with ASA, patients with aspirin-tolerant asthma, and control subjects (n= 15 in each group). Concentrations of PGE(2) in bronchoalveolar lavage fluid were measured by using ELISA. The effects of PGE(2) and EP receptor agonists on CD3/CD28-stimulated cytokine production by PBMCs were measured by using ELISA. Airways responsiveness to LTD(4)in vivo was measured in asthmatic patients by means of bronchial challenge. RESULTS: Compared with patients with aspirin-tolerant asthma, patients with ASA had increased bronchial mucosal neutrophil and eosinophil numbers but reduced percentages of T cells, macrophages, mast cells, and neutrophils expressing EP(2). Both groups showed increased bronchial sensitivity to inhaled LTD(4), but this did not correlate with mucosal expression of CysLT(1) or CysLT(2). Bronchoalveolar lavage fluid PGE(2) concentrations were comparable in all groups. In vitro PGE(2) inhibited cytokine production by PBMCs through EP(2) but not other PGE(2) receptors. CONCLUSION: Our data are consistent with the hypothesis that impaired inhibition of inflammatory leukocytes by PGE(2) acting through the EP(2) receptor has a role in the pathogenesis of ASA.
BACKGROUND: Prostaglandin E(2) (PGE(2)) is thought to play a role in the pathogenesis of aspirin-sensitive asthma (ASA). OBJECTIVE: We sought to extend our previous observations implicating impaired inflammatory cell responsiveness to PGE(2) as a pathogenetic mechanism in patients with aspirin-sensitive rhinosinusitis to the bronchial mucosa in patients with ASA. METHODS: Immunohistochemistry was used to enumerate inflammatory cells and their expression of cysteinyl leukotriene receptors 1 and 2 (CysLT(1) and CysLT(2)) and the PGE(2) receptors E-prostanoid 1 to 4 (EP(1)-EP(4)) in bronchial biopsy specimens from patients with ASA, patients with aspirin-tolerant asthma, and control subjects (n= 15 in each group). Concentrations of PGE(2) in bronchoalveolar lavage fluid were measured by using ELISA. The effects of PGE(2) and EP receptor agonists on CD3/CD28-stimulated cytokine production by PBMCs were measured by using ELISA. Airways responsiveness to LTD(4)in vivo was measured in asthmatic patients by means of bronchial challenge. RESULTS: Compared with patients with aspirin-tolerant asthma, patients with ASA had increased bronchial mucosal neutrophil and eosinophil numbers but reduced percentages of T cells, macrophages, mast cells, and neutrophils expressing EP(2). Both groups showed increased bronchial sensitivity to inhaled LTD(4), but this did not correlate with mucosal expression of CysLT(1) or CysLT(2). Bronchoalveolar lavage fluid PGE(2) concentrations were comparable in all groups. In vitro PGE(2) inhibited cytokine production by PBMCs through EP(2) but not other PGE(2) receptors. CONCLUSION: Our data are consistent with the hypothesis that impaired inhibition of inflammatory leukocytes by PGE(2) acting through the EP(2) receptor has a role in the pathogenesis of ASA.
Authors: Tao Liu; Tanya M Laidlaw; Chunli Feng; Wei Xing; Shiliang Shen; Ginger L Milne; Joshua A Boyce Journal: Proc Natl Acad Sci U S A Date: 2012-07-16 Impact factor: 11.205
Authors: Kavita Pal; Madison Ramsden; Yun M Shim; Larry Borish; Spencer C Payne; John W Steinke Journal: Ann Allergy Asthma Immunol Date: 2019-09-09 Impact factor: 6.347
Authors: Katherine N Cahill; Benjamin A Raby; Xiaobo Zhou; Feng Guo; Derek Thibault; Andreas Baccarelli; Hyang-Min Byun; Neil Bhattacharyya; John W Steinke; Joshua A Boyce; Tanya M Laidlaw Journal: Am J Respir Cell Mol Biol Date: 2016-01 Impact factor: 6.914