Histamine deficiency in gene-targeted mice strongly reduces antigen-induced airway hyper-responsiveness, eosinophilia and allergen-specific IgE.
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.
Kozma
Gergely T
GT
Department of Genetics, Cell and Immunobiology, Semmelweis University Medical School, Budapest 1445, Hungary.
Losonczy
György
G
Keszei
Márton
M
Komlósi
Zsolt
Z
Buzás
Edit
E
Pállinger
Eva
E
Appel
Judith
J
Szabó
Teréz
T
Magyar
Pál
P
Falus
András
A
Szalai
Csaba
C
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
D018925:Chemokines; D016207:Cytokines; D016210:Methacholine Chloride; D015847:Interleukin-4; D007073:Immunoglobulin E; D006632:Histamine; D007371:Interferon-gamma; D010047:Ovalbumin; D006640:Histidine Decarboxylase