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

Abstract

IntroductionBullous pemphigoid (BP) is an acquired autoimmune skin disease characterized by autoantibodies against two hemidesmosomal antigens, BP230 (BPAG1) and BP180 (BPAG2), and subepidermal blisters (1). These antihemidesmosomal autoantibodies can be detected, along with complement proteins, bound to the dermal-epidermal junction (DEJ) of perilesional skin. In the skin lesions of these patients, basal keratinocytes detach from the underlying dermis at the level of the lamina lucida, leading to subepidermal blistering (1, 2). Eosinophils (3, 4), neutrophils (5), lymphocytes (6), monocyte/macrophages (7,8), and mast cells (MCs; 7, 9) are present in the upper dermis of lesional areas in patients with BP. Interestingly, MC degranulation is a feature of BP (7, 9). Chemoattractants from MCs, including eosinophilic/neutrophilic chemotactic factors and histamine, are present at high concentrations in BP blister fluids (10, 11). Similar skin lesions are observed in the pregnancy-associated nonviral disorder herpes gestationis (12). These observations imply that MCs may play a role in blister formation.We have used an experimental model of BP that involves the passive transfer of anti-mBP180 antibodies into neonatal BALB/c mice to reproduce the key immunopathological features of this human autoimmune disease: IgG and complement deposition at the DEJ, inflammatory infiltration of the upper dermis, and subepidermal blistering (13). The pathogenicity of anti-mBP180 antibodies depends on complement activation (14) and polymorphonuclear leukocyte (PMN) recruitment (15). In the present study, we have investigated the role of MCs in experimental BP using mice genetically deficient in MCs. Preparation of pathogenic rabbit anti-mouse IgG. The preparation of recombinant mBP180 and the immunization of rabbits were performed as described previ- Methods Laboratory animals. Breeding pairs of MC-deficient WCB6F1-Mgf

Eotaxin (CCL11) and Eotaxin-2 (CCL24) Induce Recruitment of Eosinophils, Basophils, Neutrophils, and Macrophages As Well As Features of Early- and Late-Phase Allergic Reactions Following Cutaneous Injection in Human Atopic and Nonatopic Volunteers

“…The importance of mast cells in neutrophil accumulation is supported by the findings that human mast cell tryptase induces infiltration of neutrophils in guinea pig skin (28) and also stimulates the release of an IL-8-dependent neutrophil chemotactic activity from HUVEC (29). Work on a mouse model of bullous pemphigoid supports the hypothesis, as mast cells play an essential role in neutrophil recruitment during subepidermal blister formation (30).…”

Immunomodulatory mast cells: negative, as well as positive, regulators of immunity

“…67 ). Mast cells also can contribute substantially to the disease pathology in models of autoantibody-induced destructive arthritis 80 , bullous pemphigoid (an autoimmune disease of the skin) 81 and in a model of T H 17-cell-dependent, neutrophil-associated lung inflammation 68 .…”

Mouse Mast Cell Tryptase mMCP-6 Is a Critical Link between Adaptive and Innate Immunity in the Chronic Phase ofTrichinella spiralisInfection

“…Indeed, the clearest examples of mast cell responses directed by adaptive immunity are their involvement in allergic disease via stimulation by IgE (reviewed in Ref. 8) and their participation in autoantibody-driven autoimmune diseases (9,10). Aside from these pathologic states, very little else is known about the use of mast cells in the adaptive immune system directed toward clearance of chronic infections.…”