Abstract
BackgroundWhile a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation.ObjectiveTo characterize the microcirculatory events that follow mast cell degranulation.Methodology/Principal FindingsPerturbations in dermal blood flow, temperature and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI) challenge in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the histamine-associated vascular response accompanying mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an antihistamine.Conclusions/SignificanceMonitoring the hemodynamic responses within tissues that are associated with mast cell degranulation provides additional insight into the evolution of the acute inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention.
Highlights
Mast cell activation and mediator release associated with allergic inflammation is correlated with a number of immediate physiologic changes within affected tissues including bronchospasm and mucus production in the lungs; abdominal pain associated with edema and diarrhea in the gastrointestinal tract and pruritic edema in the skin [1,2,3]
Confirmation of Mast Cell Degranulation We first verified that our inducible procedures were accompanied by histamine release and that such evidence of mast cell activation correlated with the severity of the reactions
Histamine levels were compared at baseline and 10 minutes following cold hand immersion (CHI) at the peak of the vascular response in order to evaluate the histamine peak related to severity of the induced reaction
Summary
Mast cell activation and mediator release associated with allergic inflammation is correlated with a number of immediate physiologic changes within affected tissues including bronchospasm and mucus production in the lungs; abdominal pain associated with edema and diarrhea in the gastrointestinal tract and pruritic edema in the skin [1,2,3]. In spite of such observations, little is known about the direct immediate and critical effect of human mast cell degranulation on regional blood flow and the vasculature in the area of the evolving acute response. In order to better understand these vascular responses in human tissues, we chose to initiate mast cell degranulation by a physical stimulus known to activate mast cells [8]. While a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation
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