Absence of alpha4 but not beta2 integrins restrains development of chronic allergic asthma using mouse genetic models. Export

@article{citeulike:4637256, abstract = {OBJECTIVE: Chronic asthma is characterized by ongoing recruitment of inflammatory cells and airway hyperresponsiveness leading to structural airway remodeling. Although alpha4beta1 and beta2 integrins regulate leukocyte migration in inflammatory diseases and play decisive roles in acute asthma, their role has not been explored under the chronic asthma setting. To extend our earlier studies with alpha4(Delta/Delta) and beta2(-/-) mice, which showed that both alpha4 and beta2 integrins have nonredundant regulatory roles in acute ovalbumin (OVA)-induced asthma, we explored to what extent these molecular pathways control development of structural airway remodeling in chronic asthma. MATERIALS AND METHODS: Control, alpha4(Delta/Delta), and beta2(-/-) mouse groups, sensitized by intraperitoneal OVA as allergen, received intratracheal OVA periodically over days 8 to 55 to induce a chronic asthma phenotype. Post-OVA assessment of inflammation and pulmonary function (airway hyperresponsiveness), together with airway modeling measured by goblet cell metaplasia, collagen content of lung, and transforming growth factor beta1 expression in lung homogenates, were evaluated. RESULTS: In contrast to control and beta2(-/-) mice, alpha4(Delta/Delta) mice failed to develop and maintain the composite chronic asthma phenotype evaluated as mentioned and subepithelial collagen content was comparable to baseline. These data indicate that beta2 integrins, although required for inflammatory migration in acute asthma, are dispensable for structural remodeling in chronic asthma. CONCLUSION: alpha4 integrins appear to have a regulatory role in directing transforming growth factor beta-induced collagen deposition and structural alterations in lung architecture likely through interactions of Th2 cells, eosinophils, or mast cells with endothelium, resident airway cells, and/or extracellular matrix.}, author = {Banerjee, Ena Ray R. and Jiang, Yi and Henderson, William R R. and Latchman, Yvette and Papayannopoulou, Thalia}, citeulike-article-id = {4637256}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.exphem.2009.03.010}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19463772}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19463772}, doi = {10.1016/j.exphem.2009.03.010}, issn = {1873-2399}, journal = {Experimental hematology}, keywords = {asthma, lfa-1, vla-4}, month = {June}, number = {6}, posted-at = {2009-05-26 21:31:00}, priority = {2}, title = {Absence of alpha4 but not beta2 integrins restrains development of chronic allergic asthma using mouse genetic models.}, url = {http://dx.doi.org/10.1016/j.exphem.2009.03.010}, volume = {37}, year = {2009} }

TY - JOUR ID - citeulike:4637256 L3 - citeulike-article-id:4637256 N2 - OBJECTIVE: Chronic asthma is characterized by ongoing recruitment of inflammatory cells and airway hyperresponsiveness leading to structural airway remodeling. Although alpha4beta1 and beta2 integrins regulate leukocyte migration in inflammatory diseases and play decisive roles in acute asthma, their role has not been explored under the chronic asthma setting. To extend our earlier studies with alpha4(Delta/Delta) and beta2(-/-) mice, which showed that both alpha4 and beta2 integrins have nonredundant regulatory roles in acute ovalbumin (OVA)-induced asthma, we explored to what extent these molecular pathways control development of structural airway remodeling in chronic asthma. MATERIALS AND METHODS: Control, alpha4(Delta/Delta), and beta2(-/-) mouse groups, sensitized by intraperitoneal OVA as allergen, received intratracheal OVA periodically over days 8 to 55 to induce a chronic asthma phenotype. Post-OVA assessment of inflammation and pulmonary function (airway hyperresponsiveness), together with airway modeling measured by goblet cell metaplasia, collagen content of lung, and transforming growth factor beta1 expression in lung homogenates, were evaluated. RESULTS: In contrast to control and beta2(-/-) mice, alpha4(Delta/Delta) mice failed to develop and maintain the composite chronic asthma phenotype evaluated as mentioned and subepithelial collagen content was comparable to baseline. These data indicate that beta2 integrins, although required for inflammatory migration in acute asthma, are dispensable for structural remodeling in chronic asthma. CONCLUSION: alpha4 integrins appear to have a regulatory role in directing transforming growth factor beta-induced collagen deposition and structural alterations in lung architecture likely through interactions of Th2 cells, eosinophils, or mast cells with endothelium, resident airway cells, and/or extracellular matrix. IS - 6 JF - Experimental hematology SN - 1873-2399 TI - Absence of alpha4 but not beta2 integrins restrains development of chronic allergic asthma using mouse genetic models. VL - 37 KW - asthma KW - lfa-1 KW - vla-4 AU - Banerjee, Ena Ray AU - Jiang, Yi AU - Henderson, William R AU - Latchman, Yvette AU - Papayannopoulou, Thalia PY - 2009/06// UR - http://dx.doi.org/10.1016/j.exphem.2009.03.010 ER -