title: Cutting edge: histamine is required for IL-4-driven eosinophilic allergic responses.
abstract: Histamine is an important allergic mediator, and studies have defined roles for both histamine 1 and 4 receptors in allergic airway inflammation. In this study, we show that histamine is necessary to generate IL-4-driven eosinophilic inflammation, as histamine-deficient mice cannot generate eosinophilic lung inflammation in response to intratracheal IL-4 and exogenous histamine restores responsiveness. This is histamine 2 receptor (H2R) dependent because H2R knockout mice fail to respond to IL-4, and a H2R agonist restores inflammation in histidine decarboxylase knockout. Furthermore, alveolar epithelial cells require H2R to produce CCL24, an eosinophil recruitment factor, whereas H2R blockade reduces CCL24 production from wild-type cells. In an allergic inflammation model, H2R knockout mice show significantly reduced eosinophilic inflammation and CCL24 expression. These data demonstrate a previously unidentified role for H2R in allergic inflammation and establishes a synergy between endogenous histamine and IL-4 that supports eosinophilic recruitment to the lung.
authors.affiliation: Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Swartzendruber
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Byrne
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bryce
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D054423:Chemokine CCL24 / Q000096:biosynthesis; D004802:Eosinophilia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006632:Histamine / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011968:Receptors, Histamine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C515485:Ccl24 protein, mouse; D054423:Chemokine CCL24; D011968:Receptors, Histamine; D015847:Interleukin-4; D006632:Histamine