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.
