Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid
Ruoyan Chen, … , Zena Werb, Zhi Liu
Ruoyan Chen, … , Zena Werb, Zhi Liu
Published October 15, 2001
Citation Information: J Clin Invest. 2001;108(8):1151-1158. https://doi.org/10.1172/JCI11494.
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Article

Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid

Abstract

Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with an IgG autoimmune response to the hemidesmosomal protein BP180. Passive transfer of antibodies to the murine BP180 (mBP180) ectodomain triggers a blistering skin disease in mice that depends on complement activation and neutrophil infiltration and closely mimics human BP. In the present study, we show that mast cells (MCs) play a crucial role in experimental BP. Wild-type mice injected intradermally with pathogenic anti-mBP180 IgG exhibited extensive MC degranulation in skin, which preceded neutrophil infiltration and subsequent subepidermal blistering. In contrast, mice genetically deficient in MCs or MC-sufficient mice pretreated with an inhibitor of MC degranulation failed to develop BP. Further, MC-deficient mice reconstituted in skin with MCs became susceptible to experimental BP. Despite the activation of complement to yield C3a and C5a, in the absence of MCs, accumulation of neutrophils at the injection site was blunted. The lack of response due to MC deficiency was overcome by intradermal administration of a neutrophil chemoattractant, IL-8, or by reconstitution of the injection sites with neutrophils. These findings provide the first direct evidence to our knowledge that MCs play an essential role in neutrophil recruitment during subepidermal blister formation in experimental BP.

Authors

Ruoyan Chen, Gang Ning, Ming-Lang Zhao, Matthew G. Fleming, Luis A. Diaz, Zena Werb, Zhi Liu

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Experimental BP in MC-deficient mice reconstituted with normal PMNs. Pat...
Experimental BP in MC-deficient mice reconstituted with normal PMNs. Pathogenic rabbit anti-mBP180 IgG (intradermal injection, 2.5 mg/g body weight) induced skin blisters in MC-sufficient (+/+) mice (a) and toluidine blue staining showed the presence of MCs (b). Anti-mBP180 IgG failed to trigger the skin lesions in MC-deficient MgfSl/MgfSl-d mice (c), but R621 IgG triggered the skin disease in MgfSl/MgfSl-d mice reconstituted with PMNs from MC+/+ mice (e) or MC-deficient mice (data not shown). Toluidine blue staining confirmed the MC deficiency in these animals (d and f).