Mast cell fibroblastoid differentiation mediated by airway smooth muscle in asthma.
Mast cell microlocalization to the airway smooth muscle (ASM) bundle is a key feature of asthma, but whether these mast cells have an altered phenotype is uncertain. In this paper, we report that in vivo, mast cells within the ASM bundle, in contrast to mast cells in the bronchial submucosa, commonly expressed fibroblast markers and the number of these cells was closely related to the degree of airway hyperresponsiveness. In vitro human lung mast cells and mast cell lines cultured with fibronectin or with primary human ASM cells acquired typical fibroblastic markers and morphology. This differentiation toward a fibroblastoid phenotype was mediated by ASM-derived extracellular matrix proteins, independent of cell adhesion molecule-1, and was attenuated by α5β1 blockade. Fibroblastoid mast cells demonstrated increased chymase expression and activation with exaggerated spontaneous histamine release. Together these data indicate that in asthma, ASM-derived extracellular matrix proteins mediate human mast cell transition to a fibroblastoid phenotype, suggesting that this may be pivotal in the development of airway dysfunction in asthma.
Institute for Lung Health, Department of Infection, Inflammation, and Immunity, University of Leicester, Leicester, United Kingdom.
Davinder
D
Kaur
Ruth
R
Saunders
Fay
F
Hollins
Lucy
L
Woodman
Camille
C
Doe
Salman
S
Siddiqui
Peter
P
Bradding
Christopher
C
Brightling
D001249:Asthma / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D016326:Extracellular Matrix Proteins