title: Chitin elicits CCL2 from airway epithelial cells and induces CCR2-dependent innate allergic inflammation in the lung.
abstract: Chitin exposure in the lung induces eosinophilia and alternative activation of macrophages and is correlated with allergic airway disease. However, the mechanism underlying chitin-induced polarization of macrophages is poorly understood. In this paper, we show that chitin induces alternative activation of macrophages in vivo but does not do so directly in vitro. We further show that airway epithelial cells bind chitin in vitro and produce CCL2 in response to chitin both in vitro and in vivo. Supernatants of chitin-exposed epithelial cells promoted alternative activation of macrophages in vitro, whereas Ab neutralization of CCL2 in the supernate abolished the alternative activation of macrophages. CCL2 acted redundantly in vivo, but mice lacking the CCL2 receptor, CCR2, showed impaired alternative activation of macrophages in response to chitin, as measured by arginase I, CCL17, and CCL22 expression. Furthermore, CCR2 knockout mice exposed to chitin had diminished reactive oxygen species products in the lung, blunted eosinophil and monocyte recruitment, and impaired eosinophil functions as measured by expression of CCL5, IL-13, and CCL11. Thus, airway epithelial cells secrete CCL2 in response to chitin and CCR2 signaling mediates chitin-induced alternative activation of macrophages and allergic inflammation in vivo.
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: René M
authors.initials: RM
authors.lastname: Roy
authors.forename: Marcel
authors.initials: M
authors.lastname: Wüthrich
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Klein
mesh_terms: D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D002686:Chitin / Q000502:physiology*; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054390:Receptors, CCR2 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D054390:Receptors, CCR2; D002686:Chitin