Peptidase allergen Der p 1 initiates apoptosis of epithelial cells independently of tight junction proteolysis.
Loss of epithelial cell polarity, which can arise following disruption of tight junctions (TJs), is a precursor to the care-fully orchestrated removal of moribund cells from epithelia in apoptosis. Ordinarily, this cycle of events has minimally disruptive effects on the function of the epithelial barrier, but some agents have been identified that induce apoptosis and promote epithelial leakiness. The allergen Der p 1 is a cysteine peptidase that cleaves TJ adhesion proteins and induces apoptosis in epithelial cells. This suggests the possibility that, at least for some inducers of apoptosis, these events might be causally linked. We report here that Der p 1 induces epithelial apoptosis before outright cell detachment and that apoptosis occurs within the same time span as increased paracellular permeability in polarized epithelial monolayers. Whilst TJ-deficient BEAS-2B cells were resistant to Der p 1-induced apoptosis, the cell line 1HAEo-, which was also TJ deficient, was sensitive to Der p 1, providing evidence against TJ proteolysis as a cause of apoptosis. To provide direct evidence, we propagated cells that normally express TJs in low calcium medium that prevented intercellular junction assembly. These cells retained full susceptibility to Der p 1, indicating that Der p 1-induced apoptosis is independent from TJ proteolysis.
Department of Pharmacology & Clinical Pharmacology, St George's Hospital Medical School, London, UK.
Sharon F
SF
Baker
Yili
Y
Yin
Sarah K
SK
Runswick
Geoffrey A
GA
Stewart
Philip J
PJ
Thompson
David R
DR
Garrod
Clive
C
Robinson
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D039741:Antigens, Dermatophagoides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D060829:Arthropod Proteins; D001980:Bronchi / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D003546:Cysteine Endopeptidases; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D000485:Allergens; D017304:Annexin A5; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D011506:Proteins; D019014:fas Receptor; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1; D002118:Calcium