title: The Temporal Evolution of Airways Hyperresponsiveness and Inflammation.
abstract: Airways hyperresponsiveness (AHR) is usually produced within days of first antigen exposure in mouse models of asthma. Furthermore, continual antigen challenge eventually results in the resolution of the AHR phenotype. Human asthma also waxes and wanes with time, suggesting that studying the time course of AHR in the allergic mouse would offer insights into the variation in symptoms seen in asthmatics. Mice were sensitized with ovalbumin (OVA) on days 0 and 14. As assessed by airway resistance (Rn), lung elastance (H) and tissue damping (G), AHR was measured post an OVA inhalation on day 21 (Short Challengegroup), after three days of OVA inhalation on day 25 (Standard Challengegroup) and following an OVA inhalation on day 55 in mice previously challenged on days 21-23 (Recall Challengegroup). Bronchoalveolar lavage was analyzed for inflammatory cells, cytokines and protein. AHR in theShort Challengegroup was characterized by an increase inRnand neutrophil accumulation in the lavage. AHR in theStandard Challengegroup was characterized by increases inHandGbut by only a modest response inRn, while inflammation was eosinophilic. In theStandard Challengeprotocol, mice lacking fibrinogen were no different from control in their AHR response. AHR in theRecall Challengegroup was characterized by increases only inGandHand elevated numbers of both neutrophils and eosinophils. Lavage cytokines were only elevated in theRecall Challengegroup. Lavage protein was significantly elevated in all groups. The phenotype in allergically inflamed mice evolves distinctly over time, both in terms of the nature of the inflammation and the location of the AHR response. The study of mouse models of AHR might be better served by focusing on this variation rather than simply on a single time point at which AHR is maximal.
authors.affiliation: Bassett Medical Center, Cooperstown, NY, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Riesenfeld
authors.forename: Gilman B
authors.initials: GB
authors.lastname: Allen
authors.forename: Jason Ht
authors.initials: JH
authors.lastname: Bates
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Poynter
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Steven
authors.initials: S
authors.lastname: Aimiand
authors.forename: Lennart Ka
authors.initials: LK
authors.lastname: Lundblad
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