The respiratory epithelium is a specialized tissue lining the conducting airways, extending from the nasal cavity down to the bronchioles. This lining is classified as a pseudostratified columnar epithelium, meaning it appears layered under a microscope, but all cells rest on the basement membrane. Its primary function is to serve as a barrier, protecting the delicate lung tissue from inhaled particles, pathogens, and environmental toxins. The effectiveness of this protective layer depends on the coordinated actions of distinct cell types, each contributing a specialized function to maintain airway health.
Ciliated Cells and Mucociliary Escalator Function
Ciliated cells are the most abundant cell type in the trachea and bronchi, characterized by their tall, columnar shape and dense covering of rhythmic, hair-like projections called cilia. Each of these cells can possess up to 200 cilia, which extend into the airway lumen and coordinate their movement in a synchronized, wave-like pattern known as a metachronal wave. This coordinated beating is the motive force behind the mucociliary escalator, a major mechanism of innate pulmonary defense. The cilium movement occurs in a two-part cycle: a rapid, stiff power stroke that contacts the overlying mucus layer and propels it forward, followed by a slower, flexible recovery stroke that returns the cilium to its starting position beneath the mucus. This action effectively moves the mucus blanket, saturated with trapped debris, continuously upward toward the pharynx, where it is then swallowed and neutralized by stomach acid. This continuous mechanical clearance ensures the healthy lung is cleared in less than 24 hours. The efficiency of the mucociliary escalator relies on the periciliary liquid layer, which surrounds the cilia, allowing them to beat freely. Disruptions to the cilia’s structure or the fluid’s composition can severely compromise the lung’s ability to self-clean.
Goblet Cells and Protective Mucus Production
Interspersed among the ciliated cells are specialized, flask-shaped secretory cells known as goblet cells. These cells are dedicated to synthesizing and releasing the main component of the airway’s protective barrier: the mucus blanket. They accomplish this by producing and storing large, gel-forming glycoproteins called mucins, primarily Mucin 5AC (MUC5AC). Upon stimulation by irritants or pathogens, goblet cells rapidly discharge these mucins through a process of exocytosis, releasing their contents onto the epithelial surface. The mucins quickly hydrate and expand, forming the viscous, gel-like layer that sits atop the periciliary fluid. This sticky layer functions as a physical trap, capturing inhaled foreign particles, bacteria, and viruses before they can reach the lung tissue. The secreted mucus also contains various immune components, including antibodies and antimicrobial proteins, enhancing its ability to neutralize captured pathogens. The viscosity and elasticity of this mucus are tuned to facilitate its movement by the underlying cilia. However, in chronic inflammatory conditions, the number of goblet cells can increase, leading to an overproduction of thick mucus that overwhelms the ciliary clearance mechanism.
Basal Cells The Epithelium’s Stem Cell Pool
Basal cells are small, pyramid-shaped cells located at the base of the respiratory epithelium, firmly attached to the underlying basement membrane. They are the sole progenitor cell population within the pseudostratified epithelium. Their function is to act as a reserve of stem cells, preserving the integrity and regenerative capacity of the airway lining. Under normal conditions, the epithelium has a slow turnover rate, and basal cells remain relatively quiescent. When the airway lining sustains damage, these cells become activated. They rapidly proliferate and migrate to cover the damaged areas, initiating the repair process. Following proliferation, the activated basal cells differentiate into the other specialized epithelial cell types, primarily new ciliated cells and secretory goblet cells. This mechanism ensures that the functional barrier is fully restored after injury.
Specialized Cells in Airway Regulation
Beyond the three most numerous types, the respiratory epithelium contains specialized cells that perform regulatory and sensory functions. One such cell is the Club cell, formerly known as the Clara cell, which is prevalent in the smaller airways (bronchioles) where goblet and basal cells become scarce. Club cells have a dome-shaped apical surface and secrete a variety of proteins, including a surfactant-like agent that helps prevent the small airways from collapsing during breathing. These cells also possess a detoxification system containing high concentrations of cytochrome P450 enzymes. This system allows Club cells to metabolize and neutralize airborne toxins. In the bronchioles, Club cells also possess progenitor capacity, helping to regenerate the local epithelial lining when damaged.
Pulmonary Neuroendocrine Cells (PNECs)
Another rare population is the Pulmonary Neuroendocrine Cell (PNEC), which accounts for less than 0.5% of the total epithelial cells. PNECs blend neural and endocrine characteristics, acting as chemosensors that monitor the internal environment, particularly responding to changes in oxygen levels (hypoxia). These cells contain dense-core vesicles and release potent neuropeptides and neurotransmitters, such as calcitonin gene-related peptide (CGRP) and Serotonin, to regulate local processes. By releasing these bioactive molecules, PNECs can influence the tone of the smooth muscle surrounding the airways, contributing to bronchoconstriction or dilation, and coordinating immune responses. They are the only epithelial cells directly innervated by sensory neurons, providing a pathway for the lung to communicate environmental changes to the central nervous system. Their proliferation is implicated in several chronic respiratory diseases.
Brush Cells
Brush cells, also called tuft cells, function as chemosensory detectors that monitor the chemical composition of the airway surface fluid. These cells utilize the canonical taste transduction pathway, expressing Type 2 taste receptors (T2Rs) and associated signaling molecules like Gα-gustducin, to detect noxious “bitter” compounds and bacterial quorum-sensing molecules. Upon detecting these irritants, brush cells release the neurotransmitter acetylcholine. The released acetylcholine acts on nearby nerve fibers or adjacent ciliated cells, triggering protective reflexes like a reduction in breathing frequency or an increase in ciliary beat frequency. This rapid signaling mechanism provides an immediate, localized defense against potentially harmful substances, effectively linking chemical detection on the epithelial surface to an immediate physiological response. Brush cells represent a stable population that plays a direct role in regulating airway clearance and respiratory reflexes.