title: Mast cells: a pivotal role in pulmonary fibrosis.
abstract: Pulmonary fibrosis is characterized by an inflammatory response that includes macrophages, neutrophils, lymphocytes, and mast cells. The purpose of this study was to evaluate whether mast cells play a role in initiating pulmonary fibrosis. Pulmonary fibrosis was induced with bleomycin in mast-cell-deficient WBB6F1-W/W(v) (MCD) mice and their congenic controls (WBB6F1-(+)/(+)). Mast cell deficiency protected against bleomycin-induced pulmonary fibrosis, but protection was reversed with the re-introduction of mast cells to the lungs of MCD mice. Two mast cell mediators were identified as fibrogenic: histamine and renin, via angiotensin (ANG II). Both human and rat lung fibroblasts express the histamine H1 and ANG II AT1 receptor subtypes and when activated, they promote proliferation, transforming growth factor β1 secretion, and collagen synthesis. Mast cells appear to be critical to pulmonary fibrosis. Therapeutic blockade of mast cell degranulation and/or histamine and ANG II receptors should attenuate pulmonary fibrosis.
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Arul
authors.initials: A
authors.lastname: Veerappan
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: O'Connor
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Brazin
authors.forename: Alicia C
authors.initials: AC
authors.lastname: Reid
authors.forename: Albert
authors.initials: A
authors.lastname: Jung
authors.forename: David
authors.initials: D
authors.lastname: McGee
authors.forename: Barbara
authors.initials: B
authors.lastname: Summers
authors.forename: Dascher
authors.initials: D
authors.lastname: Branch-Elliman
authors.forename: Brendon
authors.initials: B
authors.lastname: Stiles
authors.forename: Stefan
authors.initials: S
authors.lastname: Worgall
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kaner
authors.forename: Randi B
authors.initials: RB
authors.lastname: Silver
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D011863:Radioimmunoassay; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D044140:Receptor, Angiotensin, Type 1; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D000804:Angiotensin II; D006632:Histamine; D003094:Collagen; D012083:Renin