Rated that dexamethasone treatment negatively modulates pro-inflammatory CXC chemokines [39]. Moreover, several authors have proved its anti-angiogenic effect [40?2]. In particular, Nakao and collaborators have shown that dexamethasone (10 mg/kg i.p.) inhibits vascular growth in a model of inflammatory corneal angiogenesis [41]. Also, Yao and colleagues have demonstrated that it reverses tracheal vessel remodeling in Mycoplasma pulmonis-infected mice (4.8 mg/day, eye drop) [42]. In the LPAL model, pretreatment with dexamethasone was effective in reducing ischemic injury at a dose even lower (1 mg/Kg) than what was previously shown to be effective in down-regulating chemokine levels [20]. However, only BAL chemokines and inflammatory cells were affected. No changes in the level of chemokine expression within bronchial tissue or, importantly, the magnitude of angiogenesis, were observed. Specifically, dexamethasone treatment resulted in significantly reduced BAL total protein, total inflammatory cells, CXCL1 protein, but not CXCL2 or macrophages. Chemokine expression in the bronchus was unchanged. Furthermore, no effects were observed at later time points either in bronchial endothelial proliferation (3 d) or bronchial perfusion of the lung (14 d). Previously, we have measured angiogenesis at late time points when a functional, perfusing vasculature was established. Although we applied the fluorescent microsphere technique in the current study as well, we also examined bronchial endothelial cell proliferation 3 d after LPAL. This additional approach aimed to quantify early angiogenesis through airway morphometry. Results showed bronchial vessels after LPAL with consistently higher numbers of PCNA+ endothelial cells than sham controls or right bronchi. However, dexamethasone treatment did not reduce such endothelial cell proliferation, nor altered angiogenesis, even with the previously shown effectiveness in limiting BAL fluid components that had access to bronchial vessels. Furthermore, early signals occurring within the bronchial niche where arteriogenesis originates, appeared not to be altered either. Based on these results, we suggest that the local bronchial tissue environment plays a critical role in inducing specific growth factors important for subsequent neovascularization during pulmonary ischemia. In summary, our results confirm the presence of CXC chemokines within BAL fluid as well as within the left mainstem bronchus. Despite significant reduction in lung injury and inflammation with dexamethasone treatment, both CXCL1 and CXCL2 chemokine expression within the bronchial tissue as well as angiogenesis were not affected. We conclude that early and specific changes within the bronchial niche selectively contribute to subsequent neovascularization during pulmonary ischemia.Author ContributionsConceived and designed the Dimethylenastron biological activity experiments: MGP EMW. Performed the experiments: MGP AM JJ EMW. Analyzed the data: MGP AM EMW. Wrote the paper: MGP EMW.Acute Ischemia and CXC Chemokines
Over the past thirty years, the mechanisms that underlie the fundamental PD168393 site processes of animal development have been identified and characterized at a molecular level in a select group of model organisms. Although the field of embryology traditionally investigated a diverse range of organisms the full power of developmental genetics has been brought to bear on developmental questions in only a few animal model systems [1?]. Elucidation of the mechanisms underlying th.Rated that dexamethasone treatment negatively modulates pro-inflammatory CXC chemokines [39]. Moreover, several authors have proved its anti-angiogenic effect [40?2]. In particular, Nakao and collaborators have shown that dexamethasone (10 mg/kg i.p.) inhibits vascular growth in a model of inflammatory corneal angiogenesis [41]. Also, Yao and colleagues have demonstrated that it reverses tracheal vessel remodeling in Mycoplasma pulmonis-infected mice (4.8 mg/day, eye drop) [42]. In the LPAL model, pretreatment with dexamethasone was effective in reducing ischemic injury at a dose even lower (1 mg/Kg) than what was previously shown to be effective in down-regulating chemokine levels [20]. However, only BAL chemokines and inflammatory cells were affected. No changes in the level of chemokine expression within bronchial tissue or, importantly, the magnitude of angiogenesis, were observed. Specifically, dexamethasone treatment resulted in significantly reduced BAL total protein, total inflammatory cells, CXCL1 protein, but not CXCL2 or macrophages. Chemokine expression in the bronchus was unchanged. Furthermore, no effects were observed at later time points either in bronchial endothelial proliferation (3 d) or bronchial perfusion of the lung (14 d). Previously, we have measured angiogenesis at late time points when a functional, perfusing vasculature was established. Although we applied the fluorescent microsphere technique in the current study as well, we also examined bronchial endothelial cell proliferation 3 d after LPAL. This additional approach aimed to quantify early angiogenesis through airway morphometry. Results showed bronchial vessels after LPAL with consistently higher numbers of PCNA+ endothelial cells than sham controls or right bronchi. However, dexamethasone treatment did not reduce such endothelial cell proliferation, nor altered angiogenesis, even with the previously shown effectiveness in limiting BAL fluid components that had access to bronchial vessels. Furthermore, early signals occurring within the bronchial niche where arteriogenesis originates, appeared not to be altered either. Based on these results, we suggest that the local bronchial tissue environment plays a critical role in inducing specific growth factors important for subsequent neovascularization during pulmonary ischemia. In summary, our results confirm the presence of CXC chemokines within BAL fluid as well as within the left mainstem bronchus. Despite significant reduction in lung injury and inflammation with dexamethasone treatment, both CXCL1 and CXCL2 chemokine expression within the bronchial tissue as well as angiogenesis were not affected. We conclude that early and specific changes within the bronchial niche selectively contribute to subsequent neovascularization during pulmonary ischemia.Author ContributionsConceived and designed the experiments: MGP EMW. Performed the experiments: MGP AM JJ EMW. Analyzed the data: MGP AM EMW. Wrote the paper: MGP EMW.Acute Ischemia and CXC Chemokines
Over the past thirty years, the mechanisms that underlie the fundamental processes of animal development have been identified and characterized at a molecular level in a select group of model organisms. Although the field of embryology traditionally investigated a diverse range of organisms the full power of developmental genetics has been brought to bear on developmental questions in only a few animal model systems [1?]. Elucidation of the mechanisms underlying th.
