title: Histamine deficiency in gene-targeted mice strongly reduces antigen-induced airway hyper-responsiveness, eosinophilia and allergen-specific IgE.
abstract: Histamine is an important mediator released from activated mast cells provoked by allergen and has a substantial role in the pathophysiology of asthma. However, several lines of evidence indicate that histamine could also have important functions in the regulation of basic cell biological processes. We have used histidine decarboxylase gene-targeted (HDC-KO) mice, lacking histamine, to investigate the effect of histamine deficiency in an animal model of asthma. Our previous investigations revealed that HDC-KO mice had fewer mast cells with reduced granular content and defective degranulation characteristics. Ovalbumin (OVA)-sensitized and challenged HDC-KO mice had significantly reduced airway hyper-responsiveness, lung inflammation, bronchoalveolar lavage eosinophilia, and OVA-specific IgE compared with congenic wild-type littermates treated in the same way. Comparing the expression profiles of cytokines, the levels of IL-1alpha, IL-1beta, IL-4, IL-5, IL-6 and IFN-gamma were significantly lower in the HDC-KO mice in asthmatic late phase, indicating a significantly altered immune response to OVA provocation and challenge. Evaluation of chemokine gene expression revealed that OVA treatment caused elevation of both T(h)1- and T(h)2-type chemokines in wild-type mice, while the chemokine expression was polarized toward a T(h)1 response in HDC-KO mice. According to our results we can suggest that the possible causes of the reduced asthma symptoms in the HDC-KO mice may be the imperfect mast and eosinophil cell system, and an altered immune response to OVA provocation and challenge.
authors.affiliation: Department of Genetics, Cell and Immunobiology, Semmelweis University Medical School, Budapest 1445, Hungary.
authors.forename: Gergely T
authors.initials: GT
authors.lastname: Kozma
authors.forename: György
authors.initials: G
authors.lastname: Losonczy
authors.forename: Márton
authors.initials: M
authors.lastname: Keszei
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Komlósi
authors.forename: Edit
authors.initials: E
authors.lastname: Buzás
authors.forename: Eva
authors.initials: E
authors.lastname: Pállinger
authors.forename: Judith
authors.initials: J
authors.lastname: Appel
authors.forename: Teréz
authors.initials: T
authors.lastname: Szabó
authors.forename: Pál
authors.initials: P
authors.lastname: Magyar
authors.forename: András
authors.initials: A
authors.lastname: Falus
authors.forename: Csaba
authors.initials: C
authors.lastname: Szalai
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001985:Bronchial Provocation Tests / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000032:analysis / Q000235:genetics; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D003627:Data Interpretation, Statistical; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D006632:Histamine / Q000378:metabolism / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000235:genetics* / Q000378:metabolism; D006651:Histocytochemistry / Q000379:methods; D007114:Immunization / Q000379:methods; D007073:Immunoglobulin E / Q000097:blood*; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016210:Methacholine Chloride / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010991:Plethysmography / Q000379:methods
chemical_list: D018925:Chemokines; D016207:Cytokines; D016210:Methacholine Chloride; D015847:Interleukin-4; D007073:Immunoglobulin E; D006632:Histamine; D007371:Interferon-gamma; D010047:Ovalbumin; D006640:Histidine Decarboxylase