According to a new study published in the American Journal of Respiratory Cell and Molecular Biology, human lungs have odor receptors.
A diagram of the airway lining suggests how the pulmonary neuroendocrine cells (red) trigger a response to inhaled chemicals. When a chemical (orange triangle) docks on a receptor (black) they dump secretory chemicals (thin orange arrows), which have an immediate but localized effect on muscles (blue) and nerves (pink), possibly triggering responses such as a cough. Image credit: Yehuda Ben-Shahar.
Unlike the receptors in human nose, which are located in the membranes of nerve cells, the ones in lungs are in the membranes of neuroendocrine cells. Instead of sending nerve impulses to the brain that allow it to perceive the acrid smell of a burning cigarette somewhere in the vicinity, they trigger the flask-shaped neuroendocrine cells to dump hormones that make airways constrict.
The newly discovered cells expressing olfactory receptors in airways are called pulmonary neuroendocrine cells (PNEC). These cells are sentinels, guards whose job it is to exclude irritating or toxic chemicals.
When a human or other mammal inhales, volatile chemicals flow over two patches of specialized epithelial tissue high up in the nasal passages. These patches are rich in nerve cells with specialized odorant-binding molecules embedded in their membranes.
If a chemical docks on one of these receptors, the neuron fires, sending impulses along the olfactory nerve to the olfactory bulb in the brain, where the signal is integrated with those from hundreds of other similar cells to conjure the scent of old leather or dried lavender.
Aware that airway diseases are characterized by hypersensitivity to volatile stimuli, study’s senior author Dr Yehuda Ben-Sharar of Washington University in St. Louis with colleagues realized that the lungs, like the nose, must have some means of detecting inhaled chemicals.
Earlier a team at the University of Iowa had searched for genes expressed by patches of tissue from lung transplant donors. They found a group of ciliated cells that express bitter taste receptors. When offending substances were detected, the cilia beat more strongly to sweep them out of the airway.
But since people are sensitive to many inhaled substances, not just bitter ones, Dr Ben-Shahar’s team decided to look again. This time they found that these tissues also express odor receptors, not on ciliated cells but instead on neuroendocrine cells, flask-shaped cells that dump serotonin and various neuropeptides when they are stimulated.
The flask-like pulmonary neuroendocrine cells that are full of serotonin (stained green here) and other chemicals extend processes up through the epithelial cells (purple) lining the airways to monitor the chemical makeup of each breath. The top part of the image is a plan view of the airway lining and the bottom part is a section through the lining. Image credit: Yehuda Ben-Shahar.
“This made sense. When people with airway disease have pathological responses to odors, they’re usually pretty fast and violent. Patients suddenly shut down and can’t breath and these cells may explain why,” Dr Ben-Shahar said.
“There are the differences between chemosensation in the nose and in the lung. The cells in the nose are neurons, each with a narrowly tuned receptor, and their signals must be woven together in the brain to interpret our odor environment.”
The cells in the airways are secretory not neuronal cells and they may carry more than one receptor, so they are broadly tuned. Instead of sending nerve impulses to the brain, they flood local nerves and muscles with serotonin and neuropeptides.
Dr Ben-Shahar added: “they are possibly designed to elicit a rapid, physiological response if you inhale something that is bad for you.”
The different mechanisms explain why cognition plays a much stronger role in taste and smell than in coughing in response to an irritant. It is possible, for example, to develop a taste for beer. But nobody learns not to cough; the response is rapid and largely automatic.
The scientists suspect these pulmonary neuroscretory cells contribute to the hypersensitivity of patients with chronic obstructive pulmonary disease to airborne irritants.
When the scientists looked at the airway tissues from patients with chronic obstructive pulmonary disease they discovered that they had more of these neurosecretory cells than airway tissues from healthy donors.
The scientists are hopeful that the PNEC pathways will provide targets for drugs that would better control asthma, chronic obstructive pulmonary disease and other respiratory diseases.
______
Xiaoling Gu et al. Volatile-Sensing Functions for Pulmonary Neuroendocrine Cells. American Journal of Respiratory Cell and Molecular Biology, published online October 17, 2013; doi: 10.1165/rcmb.2013-0199OC
