Monocytes enhance neutrophil-induced blister formation in an ex vivo model of bullous pemphigoid.

de Graauw, E; Sitaru, C; Horn, Michael; Borradori, Luca; Yousefi, Shida; Simon, Dagmar; Simon, Hans-Uwe (2018). Monocytes enhance neutrophil-induced blister formation in an ex vivo model of bullous pemphigoid. Allergy, 73(5), pp. 1119-1130. Wiley-Blackwell 10.1111/all.13376

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BACKGROUND Lesions of bullous pemphigoid (BP), an autoimmune subepidermal blistering disease characterized by the presence of tissue-bound and circulating autoantibodies to hemidesmosomal antigens, harbor a mixed inflammatory cellular infiltrate. In various models, neutrophils, eosinophils, mast cells, monocytes as well as B and T cells have been shown to be involved in the pathogenesis of BP. However, their interactions with and effective role in blister formation remain uncertain. This study was aimed at investigating the effect of monocyte/neutrophil interaction on blister formation in an ex vivo BP model. METHODS Skin cryosections were incubated with purified human neutrophils and monocytes, in the presence or absence of BP autoantibodies. Production of reactive oxygen species (ROS), degranulation, mediator release (neutrophil elastase [NE], myeloperoxidase [MPO], matrix metalloproteinase-9 [MMP-9]), binding of Fcγ receptor (CD16, CD32, CD64), and cell adhesion (CD18, ICAM-1) was investigated using appropriate inhibitors. Dermal-epidermal separation (DES) was assessed by light microscopy and quantified by Fiji software. RESULTS Monocytes and neutrophils synergistically interact resulting in a significantly higher DES compared to either monocytes or neutrophils separately (P < .0001). Monocyte/neutrophil-induced DES was associated with increased ROS production and was dependent on adhesion and FcγRIII binding. Upon stimulation by the granule-poor fraction of monocyte supernatants, neutrophils increased their release of MMP-9, thereby also DES at the dermal-epidermal junction of skin cryosections. CONCLUSION Our observations suggest that the interaction of cells, as shown here for monocytes and neutrophils, enhances mediator release resulting in an increased subepidermal blister formation. Thus, blocking intercellular cross talk promises a new therapeutic approach for blocking tissue damage in BP.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Horn, Michael; Borradori, Luca; Yousefi, Shida; Simon, Dagmar and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0105-4538

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Sandra Nyffenegger

Date Deposited:

09 Feb 2018 13:15

Last Modified:

28 May 2018 13:03

Publisher DOI:

10.1111/all.13376

PubMed ID:

29222810

Uncontrolled Keywords:

bullous pemphigoid intercellular cross talk matrix metalloproteinases monocytes neutrophils

BORIS DOI:

10.7892/boris.110141

URI:

https://boris.unibe.ch/id/eprint/110141

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