Olfactory receptors in human airway epithelia

Olfactory receptors (OR) represent one of the largest gene families in the human genome. In spite of a signi fi cant progress in deciphering the physiological functions of olfactory receptors, how the majority of these G-protein-coupled receptors are activated is still mostly a mystery. Consequently, for the majority of OR genes there are currently no assigned physiological or behavioral functions. Deciphering ligand speci fi cities and physiological signi fi cance of human ORs is important for understanding how the human olfactory genome encodes odors, and how such odors drive human behavior in health and disease. Although OR genes were originally thought to be restricted to the olfactory epithelium, several recent studies indicated that some members of the OR family might be acting outside the canonical chemosensory system. In a recent study, we have shown that the human airway epithelial cells can also act as chemosensory cells by directly sensing the inhalation of noxious bitter compounds, which can lead to increased mucociliary clearance, and hence may serve as a protective mechanism against inhaled toxins and microorganisms. Whether the airway epithelium can detect chemicals via other sensory pathways has not been reported to date. As a step in this direction, we describe methods for studying the cellular and subcellular localization of olfactory receptor proteins and mRNAs in human airways in both primary in vitro cultures and tissue sections.