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Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function
Robert J Lee1,2, Alan D Workman1, Ryan M Carey1
1Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Aflatoxins from Aspergillus flavus impair airway cilia function, reducing ciliary beat frequency and nitric oxide production. This mycotoxin exposure may contribute to fungal respiratory diseases like invasive aspergillosis.
Area of Science:
- Respiratory Medicine
- Mycology
- Cell Physiology
Background:
- Aflatoxins, mycotoxins from Aspergillus flavus, are implicated in respiratory infections.
- Aspergillus flavus is a significant cause of invasive aspergillosis.
- Respiratory pathogens often secrete toxins that compromise mucociliary immunity.
Purpose of the Study:
- To investigate the impact of acute aflatoxin exposure on human airway cell physiology.
- To determine the effects on ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO) production.
Main Methods:
- Utilized air-liquid interface cultures of primary human sinonasal and bronchial cells.
- Measured ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO).
- Assessed protein kinase C (PKC) activity using a fluorescent reporter in A549 cells.
Main Results:
- Aflatoxin exposure reduced baseline and stimulated CBF by 6-12%.
- Conditioned media from Aspergillus species reduced CBF, with effects blocked by anti-aflatoxin antibodies for A. flavus.
- AFB2 reduced NO production by approximately 50% and activated PKC.
Conclusions:
- Aflatoxins secreted by respiratory Aspergillus flavus can impair airway cilia motility and chemosensory functions.
- These effects may contribute to the pathogenesis of fungal airway diseases.
- PKC activation is involved in aflatoxin-induced CBF reduction, but calcium and NO changes are not the primary mechanism for CBF impairment, except for AFB2's effect on NO production.
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