title: Eosinophils are necessary for pulmonary arterial remodeling in a mouse model of eosinophilic inflammation-induced pulmonary hypertension.
abstract: There is increasing evidence that inflammation plays a pivotal role in the pathogenesis of some forms of pulmonary hypertension (PH). We recently demonstrated that deficiency of adiponectin (APN) in a mouse model of PH induced by eosinophilic inflammation increases pulmonary arterial remodeling, pulmonary pressures, and the accumulation of eosinophils in the lung. Based on these data, we hypothesized that APN deficiency exacerbates PH indirectly by increasing eosinophil recruitment. Herein, we examined the role of eosinophils in the development of inflammation-induced PH. Elimination of eosinophils in APN-deficient mice by treatment with anti-interleukin-5 antibody attenuated pulmonary arterial muscularization and PH. In addition, we observed that transgenic mice that are devoid of eosinophils also do not develop pulmonary arterial muscularization in eosinophilic inflammation-induced PH. To investigate the mechanism by which APN deficiency increased eosinophil accumulation in response to an allergic inflammatory stimulus, we measured expression levels of the eosinophil-specific chemokines in alveolar macrophages isolated from the lungs of mice with eosinophilic inflammation-induced PH. In these experiments, the levels of CCL11 and CCL24 were higher in macrophages isolated from APN-deficient mice than in macrophages from wild-type mice. Finally, we demonstrate that the extracts of eosinophil granules promoted the proliferation of pulmonary arterial smooth muscle cells in vitro. These data suggest that APN deficiency may exacerbate PH, in part, by increasing eosinophil recruitment into the lung and that eosinophils could play an important role in the pathogenesis of inflammation-induced PH. These results may have implications for the pathogenesis and treatment of PH caused by vascular inflammation.
authors: Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, 02114, USA.
authors: M
authors: M
authors: Weng
authors: D M
authors: DM
authors: Baron
authors: K D
authors: KD
authors: Bloch
authors: A D
authors: AD
authors: Luster
authors: J J
authors: JJ
authors: Lee
authors: B D
authors: BD
authors: Medoff
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D002457:Cell Extracts / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000235:genetics / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054423:Chemokine CCL24 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology*; D055786:Gene Knockout Techniques; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D015848:Interleukin-5 / Q000037:antagonists & inhibitors; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D010047:Ovalbumin; D061251:Primary Cell Culture; D011651:Pulmonary Artery / Q000473:pathology*; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000150:complications*; D014158:Transcription, Genetic
chemical_list: D052242:Adiponectin; D000906:Antibodies; C515457:Ccl11 protein, mouse; C491768:Ccl2 protein, mouse; C515485:Ccl24 protein, mouse; D002457:Cell Extracts; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054423:Chemokine CCL24; D015848:Interleukin-5; D008934:Mitogens; D010047:Ovalbumin