title: House dust mite Dermatophagoides farinae augments proinflammatory mediator productions and accessory function of alveolar macrophages: implications for allergic sensitization and inflammation.
abstract: In this study, we examine the effects of Dermatophagoides farinae (Der f), a major source of airborne allergens, on alveolar macrophages (AMs), and we also test its contribution to allergic responses in mice. Der f activated NF-kappaB of AMs and, unlike OVA or LPS stimulation, up-regulated IL-6, TNF-alpha, and NO. In addition, it down-regulated antioxidants, but affected neither the expression nor production of IL-12. Der f-stimulated AMs expressed enhanced levels of costimulatory B7 molecules, supported T cell proliferation, and promoted Th2 cell development. The enhanced accessory function was suppressed by blockade mAbs to B7.2, IL-6, and TNF-alpha and by N-monomethyl-L-arginine, an NO synthase inhibitor, and N-acetylcysteine, a thiol antioxidant, whereas it was augmented by (+/-)-S-nitroso-N-acetylpenicillamine, an NO donor. Arg-Gly-Asp-Ser peptide and neo-glycoproteins galactose-BSA and mannose-BSA inhibited the Der f-induced IL-6 and TNF-alpha productions and enhanced accessory function of AMs. Der f was more potent than OVA for inducing pulmonary eosinophilic inflammation, NO, and serum allergen-specific IgG1 Ab production in mice. AMs from Der f-challenged mice expressed enhanced levels of B7 and augmented T cell proliferation ex vivo. In Der f-challenged mice, respiratory syncytial virus infection (5 x 10(5) pfu; 3 days before Der f instillation) augmented Der f-specific Ab production, whereas dexamethasone (50 mg/kg; 1 h before Der f instillation) diminished the allergic airway inflammation and Ab response. We conclude that AMs are sensitive targets for Der f and that the Der f-induced proinflammatory responses may represent an important mechanism in mediating the development of allergic sensitization and inflammation.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
authors.forename: Chih-Long
authors.initials: CL
authors.lastname: Chen
authors.forename: Chen-Ting
authors.initials: CT
authors.lastname: Lee
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Liu
authors.forename: Jiu-Yao
authors.initials: JY
authors.lastname: Wang
authors.forename: Huan-Yao
authors.initials: HY
authors.lastname: Lei
authors.forename: Chun-Keung
authors.initials: CK
authors.lastname: Yu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology*; D000485:Allergens / Q000276:immunology / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology*; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D040001:Dermatophagoides farinae / Q000276:immunology*; D003907:Dexamethasone / Q000008:administration & dosage; D004391:Dust / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology; D007106:Immune Sera / Q000096:biosynthesis; D007114:Immunization; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018836:Inflammation Mediators / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007442:Intubation, Intratracheal; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D015703:Antigens, CD; D039741:Antigens, Dermatophagoides; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D004391:Dust; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D007106:Immune Sera; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D009569:Nitric Oxide; D003907:Dexamethasone; C046617:arginyl-glycyl-aspartyl-serine