title: Elemental signals regulating eosinophil accumulation in the lung.
abstract: In this review we identify the elemental signals that regulate eosinophil accumulation in the allergic lung. We show that there are two interwoven mechanisms for the accumulation of eosinophils in pulmonary tissues and that these mechanisms are linked to the development of airways hyperreactivity (AHR). Interleukin-(IL)-5 plays a critical role in the expansion of eosinophil pools in both the bone marrow and blood in response to allergen provocation of the airways. Secondly, IL-4 and IL-13 operate within the allergic lung to control the transmigration of eosinophils across the vascular bed into pulmonary tissues. This process exclusively promotes tissue accumulation of eosinophils. IL-13 and IL-4 probably act by activating eosinophil-specific adhesion pathways and by regulating the production of IL-5 and eotaxin in the lung compartment. IL-5 and eotaxin co-operate locally in pulmonary tissues to selectively and synergistically promote eosinophilia. Thus, IL-5 acts systemically to induce eosinophilia and within tissues to promote local chemotactic signals. Regulation of IL-5 and eotaxin levels within the lung by IL-4 and IL-13 allows Th2 cells to elegantly co-ordinate tissue and peripheral eosinophilia. Whilst the inhibition of either the IL-4/IL-13 or IL-5/eotaxin pathways resulted in the abolition of tissue eosinophils and AHR, only depletion of IL-5 and eotaxin concurrently results in marked attenuation of pulmonary inflammation. These data highlight the importance of targeting both IL-5 and CCR3 signalling systems for the resolution of inflammation and AHR associated with asthma.
authors: Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Acton, Canberra ACT. Paul.Foster@anu.edu.au
authors: P S
authors: PS
authors: Foster
authors: A W
authors: AW
authors: Mould
authors: M
authors: M
authors: Yang
authors: J
authors: J
authors: Mackenzie
authors: J
authors: J
authors: Mattes
authors: S P
authors: SP
authors: Hogan
authors: S
authors: S
authors: Mahalingam
authors: A N
authors: AN
authors: Mckenzie
authors: M E
authors: ME
authors: Rothenberg
authors: I G
authors: IG
authors: Young
authors: K I
authors: KI
authors: Matthaei
authors: D C
authors: DC
authors: Webb
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology; D002448:Cell Adhesion; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000502:physiology*; D004804:Eosinophils; D006801:Humans; D007167:Immunotherapy; D007249:Inflammation; D018793:Interleukin-13 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000503:physiopathology*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology
chemical_list: C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4