title: Activation and regulation of chemokines in allergic airway inflammation.
abstract: Allergic airway inflammation is characterized by peribronchial eosinophil accumulation with the submucosa surrounding the airway. The initial induction of immunoglobulin E (IgE)-mediated mast cell degranulation, up-regulation of adhesion molecules, and the production of inflammatory and chemotactic cytokines, leading to the infiltration of specific leukocyte subsets, is orchestrated in a sequential manner. The activation and degranulation of local mast cell populations is an immediate airway response mediated both by antigen-specific, surface bound IgE and by cytokine-induced activational pathways. Subsequently the infiltration and activation of effector leukocytes (neutrophils and eosinophils) mediated by the persistent activation of allergen-specific T cells leads to pathological manifestations within the lung and airway. The development of appropriate animal models to dissect the critical mechanisms involved in antigen-induced airway pathology is crucial for the development of efficacious therapies. We have utilized a model of allergic airway inflammation induced by intratracheal challenge with parasite (Schistosoma mansoni) egg antigen in presensitized mice. This model has proven useful in the assessment of eosinophil recruitment and has identified key cytokines involved in leukocyte elicitation. These cytokines include interleukin-4 and elicitation. These cytokines include interleukin-4 and tumor necrosis factor, which appear to act as early response mediators, as well as C-C chemokines, macrophage inflammatory protein-1a, and RANTES, which act directly on eosinophil recruitment. In addition, we have found that both C-X-C and C-C chemokines are expressed in pulmonary-derived mast cells, suggesting an important contribution to leukocyte responses in the allergic airway.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, USA.
authors.forename: N W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
authors.forename: S W
authors.initials: SW
authors.lastname: Chensue
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology*; D018925:Chemokines / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism* / Q000473:pathology*
chemical_list: D018925:Chemokines