Cigarette smoke total particulate matter increases mucous secreting cell numbers in vitro: a potential model of goblet cell hyperplasia.
Cigarette smoking is associated with chronic obstructive pulmonary disease (COPD)--a term encompassing chronic lung inflammation, chronic bronchitis and emphysema. Goblet cell hyperplasia is a characteristic feature of the lung epithelium in COPD patients contributing to the overproduction of airway mucus, including mucin MUC5AC. Using an in vitro model of differentiated lung epithelium we have investigated morphological and cellular changes in response to interleukin (IL)-13 (2.5-20 ng/ml), cigarette smoke total particulate matter (TPM; 0.31-20 microg/ml) and three mainstream cigarette smoke constituents: acrolein, formaldehyde and acetaldehyde (all at 0.001-1 microM) over 28 days during differentiation (agents replaced daily Monday-Friday). Control cultures of human bronchial epithelial cells (HBECs) underwent mucociliary differentiation producing a columnar epithelium containing goblet, ciliated and basal cells. Non-cytotoxic doses of IL-13 induced a significant increase in the percentage of MUC5AC positive cells. Using both flow cytometry and immunocytochemical techniques for identification of MUC5AC positive cells, TPM treatment induced an increase in MUC5AC positive cells, becoming maximal at 5 microg/ml. Acrolein treatment also increased the percentage of MUC5AC positive cells. However, formaldehyde or acetaldehyde had little effect. This study demonstrates that lung toxicants can induce a profound effect on cellular differentiation in an in vitro model of the human lung epithelium.
Haswell
Linsey E
LE
British American Tobacco, Group R&D, Regents Park Road, Southampton SO15 8TL, UK.
Hewitt
Katherine
K
Thorne
David
D
Richter
Audrey
A
Gaça
Marianna D
MD
D000079:Acetaldehyde / Q000633:toxicity; D000171:Acrolein / Q000633:toxicity; D000328:Adult; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents; D017097:Electric Impedance; D005434:Flow Cytometry; D005557:Formaldehyde / Q000633:toxicity; D020397:Goblet Cells / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000096:biosynthesis; D008854:Microscopy, Electron; D055271:Mucin 5AC / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D009499:Neutral Red; D052638:Particulate Matter / Q000633:toxicity*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000633:toxicity*
D004396:Coloring Agents; D018793:Interleukin-13; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D052638:Particulate Matter; D012906:Smoke; D005557:Formaldehyde; D009499:Neutral Red; D000171:Acrolein; D000079:Acetaldehyde