Experimental Effect of Cigarette Smoke on Human Respiratory Cilia

Histone deacetylase 6–mediated selective autophagy regulates COPD-associated cilia dysfunction

“…The resulting disruption in mucociliary function may render the host susceptible to infection and particle-induced lung injury, which in turn may contribute to the pathogenesis of chronic bronchitis and emphysema (3,4,25,27). Although it is well established that CS exposure causes cilia shortening (25,27), the underlying cellular and molecular mechanisms for this phenomenon remain incompletely delineated. In this study, we demonstrate for what we believe to be the first time that CS can induce cilia shortening through an autophagy-dependent mechanism mediated by HDAC6, a process we term "ciliophagy" (Figure 10).…”

“…Disruption of airway epithelial cell function upon CS exposure results in impaired mucociliary clearance (MCC) (25)(26)(27). In patients with COPD, impaired airway clearance may promote susceptibility to respiratory infections (2).…”

“…In patients with COPD, impaired airway clearance may promote susceptibility to respiratory infections (2). Disruption of MCC in response to CS exposure is attributed to a reduction in epithelial cell cilia length and airway epithelial cell death (4,(25)(26)(27), followed by reepithelialization dominated by goblet cells, resulting in excess mucus production (28). The mechanisms by which CS-induced epithelial cell dysfunction leads to cilia shortening and altered airway function in vivo remain unclear.…”

Smoking Is Associated with Shortened Airway Cilia.

“…The actual depth of the airway surface fluid is reported to be 6 to 7 mm [43][44][45][46][47]. In this range, the shorter cilia in smokers would result in a reduction of effective cilia of approximately 18 to 38%, consistent with the data that smokers have a decreased mucociliary clearance compared to nonsmokers [1,7,8,[18][19][20][21][22][23][24].…”

“…One critical component is cilia, the hair-like projections on airway epithelial cells that move in metachronal waves and work in conjunction with mucus to clear the airway of inhaled particulates [9,[14][15][16][17]. Several reports demonstrate that cigarette smoke reduces ciliary beat frequency and interrupts the intercellular coordination of the metachronal waves [18][19][20][21][22][23][24], and ultrastructural studies have documented smoking-associated increased incidence of structural defects in cilia, including missing radial spokes, nexin links, central sheath, outer and inner dynein arms, and central microtubules, as well as more peripheral doublets and fused cilia [25][26][27][28][29][30][31][32][33][34].…”