Activation of mast cells is essential for development of house dust mite Dermatophagoides farinae-induced allergic airway inflammation in mice.
In this study, we demonstrate that Dermatophagoides farinae (Der f), a major source of airborne allergens, but not OVA, could rapidly activate mast cells in mice. This was indicated by an elevation of serum mouse mast cell protease 1, a mast cell-specific proteinase, as early as 30 min after intratracheal challenge. Administration of sodium cromoglycate (40 mg/kg, i.p., 1 h before Der f instillation), a mast cell stabilizer, not only suppressed acute mouse mast cell protease 1 production but also attenuated the allergic airway inflammation provoked by repetitive Der f challenge in mice (five times at 1-wk interval). Der f induced the expression of mRNA for TNF-alpha, IL-1beta, IL-4, IL-6, IL-9, and IL-13 in mastocytoma P815 cells and stimulated both P815 cells and bone marrow-derived mast cells to produce IL-4, IL-6, and TNF-alpha in a dose- and time-dependent manner. Cycloheximide as well as sodium cromoglycate blocked the Der f-induced IL-4 production, indicating a de novo protein synthesis process. Supernatants of Der f-stimulated mast cells chemoattracted monocytes and T lymphocytes; they up-regulated the expression of costimulatory B7 molecules, eotaxin, RANTES, monocyte chemoattractant protein 1, and IFN-inducible protein 10 mRNA of alveolar macrophages; they supported PHA-induced T cell proliferation; and they promoted Th2 cell development. Our data indicate that mast cells may be an important cell type during the initiation of Der f sensitization in the airway by modulating the function of alveolar macrophages and T cells.
D000485:Allergens / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D002455:Cell Division / Q000276:immunology; D045744:Cell Line, Tumor; D002474:Cell-Free System / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D040001:Dermatophagoides farinae / Q000276:immunology*; D004391:Dust / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007442:Intubation, Intratracheal; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000485:Allergens; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D018925:Chemokines; D016207:Cytokines; D004391:Dust; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins