Eosinophil peroxidase induces the expression and function of acid-sensing ion channel-3 in allergic rhinitis:in vitro evidence in cultured epithelial cells

BACKGROUND:
Acid-sensing ion channels (ASIC) are a family of acid-activated ligand-gated cation channels. As tissue acidosis is a feature of inflammatory conditions, such as allergic rhinitis (AR), we investigated the expression and function of these channels in AR.
OBJECTIVES:
The aim of the study was to assess expression and function of ASIC channels in the nasal mucosa of control and AR subjects.
METHODS:
Immunohistochemical localization of ASIC receptors and functional responses to lactic acid application were investigated. In vitro studies on cultured epithelial cells were performed to assess underlying mechanisms of ASIC function.
RESULTS:
Lactic acid at pH 7.03 induced a significant rise in nasal fluid secretion that was inhibited by pre-treatment with the ASIC inhibitor amiloride in AR subjects (n = 19). Quantitative PCR on cDNA isolated from nasal biopsies from control and AR subjects demonstrated that ASIC-1 was equally expressed in both populations, but ASIC-3 was significantly more highly expressed in AR (P < 0.02). Immunohistochemistry confirmed significantly higher ASIC-3 protein expression on nasal epithelial cells in AR patients than controls (P < 0.01). Immunoreactivity for EPO+ eosinophils in both nasal epithelium and submucosa was more prominent in AR compared with controls. A mechanism of induction of ASIC-3 expression relevant to AR was suggested by the finding that eosinophil peroxidase (EPO), acting via ERK1/2, induced the expression of ASIC-3 in epithelial cells. Furthermore, using a quantitative functional measure of epithelial cell secretory function in vitro, EPO increased the air-surface liquid depth via an ASIC-dependent chloride secretory pathway.
CONCLUSIONS:
This data suggests a possible mechanism for the observed association of eosinophils and rhinorrhoea in AR and is manifested through enhanced ASIC-3 expression.

Hidden Contradictions and Conditionality: Conceptualisations of Inclusive Education in International Law

The nature of education that children with disabilities should receive has been subject to much debate. This article critically assesses the ways in which the international human rights framework has conceptualised ‘inclusive education’. It argues that the right to education for children with disabilities in international law is constitutive of hidden contradictions and conditionality. This is most evident with respect to conceptualisations of ‘inclusion’ and ‘support’, and their respective emphases upon the extent of individual impairment or ‘deficit’ rather than upon the extent of institutional or structural deficit. It is vital that the new Committee on the Rights of Persons with Disabilities pays close attention to the utilisation of these concepts lest the Convention on the Rights of Persons with Disabilities further legitimises the ‘special needs’ educational discourse to which children with disabilities have been subject.

A Case for Humanity in the Law of Rape.

One of Irigaray’s most insistent criticisms of the operation of patriarchal law is its overwhelming focus on the protection of property at the expense of law that regulates relations between and amongst persons. This paper argues, with reference to Irigaray’s work, that the conceptual change involved in such a reorientation of law’s focus has important implications for the legal perception of the harm of rape and woman’s sexuality. The possessive paradigm operates in the law of rape by disassociating the harm of rape from its psychic and subjective impact and encouraging the ‘simple’rape/ ‘real’ rape dichotomy. In returning subjectivity to woman herself we can begin to see perhaps how the crime of rape involves a harm to woman that affects the whole of her being, and to be. Such a reading allows the law to perhaps move away from understanding rape as a violation of undifferentiated bodies to a violation of the innate ‘virginity’ of woman.