Eotaxin-Rich Proangiogenic Hematopoietic Progenitor Cells and CCR3+ Endothelium in the Atopic Asthmatic Response

• Published in: The Journal of immunology (1950) 2016-03, Vol.196 (5), p.2377-2387
• Main Authors: Asosingh, Kewal, Vasanji, Amit, Tipton, Aaron, Queisser, Kimberly, Wanner, Nicholas, Janocha, Allison, Grandon, Deepa, Anand-Apte, Bela, Rothenberg, Marc E, Dweik, Raed, Erzurum, Serpil C
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Adult; Allergens - immunology; Animals; Asthma - genetics; Asthma - metabolism; Asthma - pathology; Bone Marrow Cells - metabolism; Bone Marrow Transplantation; Case-Control Studies; Chemokine CCL11 - genetics; Chemokine CCL11 - metabolism; Chemokine CCL24 - genetics; Chemokine CCL24 - metabolism; Disease Models, Animal; Endothelial Cells - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Eosinophils - immunology; Eosinophils - metabolism; Female; Hematopoietic Stem Cells - metabolism; Humans; Hypersensitivity, Immediate - genetics; Hypersensitivity, Immediate - metabolism; Hypersensitivity, Immediate - pathology; Immunohistochemistry; Male; Mice; Mice, Knockout; Neovascularization, Pathologic - metabolism; Receptors, CCR3 - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1500770

Angiogenesis is closely linked to and precedes eosinophilic infiltration in asthma. Eosinophils are recruited into the airway by chemoattractant eotaxins, which are expressed by endothelial cells, smooth muscles cells, epithelial cells, and hematopoietic cells. We hypothesized that bone marrow-derived proangiogenic progenitor cells that contain eotaxins contribute to the initiation of angiogenesis and inflammation in asthma. Whole-lung allergen challenge of atopic asthma patients revealed vascular activation occurs within hours of challenge and before airway inflammation. The eotaxin receptor CCR3 was expressed at high levels on submucosal endothelial cells in patients and a murine model of asthma. Ex vivo exposure of murine endothelial cells to eotaxins induced migration and angiogenesis. In mechanistic studies, wild-type mice transplanted with eotaxin-1/2-deficient bone marrow had markedly less angiogenesis and inflammation in an atopic asthma model, whereas adoptive transfer of proangiogenic progenitor cells from wild-type mice in an atopic asthma model into the eotaxin-1/2-deficient mice led to angiogenesis and airway inflammation. The findings indicate that Th2-promoting hematopoietic progenitor cells are rapidly recruited to the lung upon allergen exposure and release eotaxins that coordinately activate endothelial cells, angiogenesis, and airway inflammation.