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Key Event Title
Occurrence, Hyperplasia of goblet cells
Key Event Components
Key Event Overview
AOPs Including This Key Event
Key Event Description
Goblet cell hyperplasia refers to an increase in goblet cell numbers and is a common feature of airway epithelia in asthma and other respiratory diseases. It can arise from sustained proliferation of this cell population following airway injury by, for example, exposure to allergens, pathogens, cigarette smoke and other inhalation exposures (Miyabara et al., 1998; Nagao et al., 2003; Saetta et al., 2000; van Hove et al., 2009; Walter et al., 2002; Hao et al., 2014; Lukacs et al., 2010; Hao et al., 2013; Yageta et al., 2014; Nie et al., 2012; Hegab et al., 2007; Kim et al., 2016).
How It Is Measured or Detected
Goblet cells are mucin-producing columnar epithelial cells, and their secretory granules can be identified easily by light or electron microscopy (Rogers, 1994). However, MUC5AC immunohistochemical staining is typically used to identify and enumerate this cell type in tissue sections, even though this is semi-quantitative at best. Alternatively, staining of tissue sections with Alcian blue (AB) or AB in combination with periodic acid–Schiff (PAS) can also be used to highlight and count mucus-containing goblet cells. In addition, the simultaneous detection and quantification of proliferation markers such as PCNA or Ki-67 may prove helpful in identifying proliferating goblet cells following airway injury.
In laboratory animals, GCH may be identified by a pathologist as an increase in the number of goblet cells in an epithelium which normally contains only few goblet cells (Harkema and Hotchkiss, 1993). An experienced pathologist may assign a score for the extent of GCH occurring in human airway epithelial tissues, and although no standard for this assessment exists, this appears to be a clinically accepted approach.
Domain of Applicability
Goblet cell hyperplasia (GCH) was reported in respiratory epithelia of humans, mice, rats, ferrets and dogs following various inhalation exposures (Park et al.,1977; Saetta et al., 2000; Takeyama et al., 2008; Tesfaigzi et al., 2000; Werley et al., 2016). Although GCH is a common feature of adaptation to respiratory irritants and/or airway epithelial repair among these species, some species differences exist with respect to the sensitivity toward certain exposures (Wolf et al., 1995; NTP, 1994).
Evidence for Perturbation by Stressor
Cigarette smoke exposure causes goblet cell hyperplasia in the trachea, bronchi and bronchioles of mice, rats, dogs and humans (Park et al., 1977; Saetta et al., 2000; Tesfaigzi et al., 2000; Takeyama et al., 2008; Werley et al., 2016).
Treatment of primary human bronchial epithelial cells differentiated at the air-liquid interface with up to 20 µg/mL cigarette smoke total particulate matter induced a concentration dependent increase in the percentage of MUC5A-positive cells (Haswell et al., 2010). Similarly, repeated exposure of primary human bronchial epithelial cells differentiated at the air-liquid interface to smoke from 1R6F reference cigarettes (University of Kentucky) 3 times per week for up to 6 weeks significantly increased the MUC5AC-positive cell population starting from week 4 (Haswell et al., 2021).
Treatment of primary human bronchial epithelial cells differentiated at the air-liquid interface with up to 1 µM acrolein induced a concentration dependent increase in the percentage of MUC5A-positive cells (Haswell et al., 2010).
Goblet cell numbers increased in a time-dependent manner in ovalbumin-sensitized mice (sensitized on days 1 and 14 by intraperitoneal injection of 10 μg ovalbumin and 1 mg of aluminum potassium sulfate in 500 μL of saline solution, and challenged on days 21 to 23 by daily 30-min exposure to aerosolized 1% (wt/vol) ovalbumin) that were whole-body exposed to 2 ppm ozone for 4, 8, and 12 weeks (Jang et al., 2006).
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