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Titolo:
The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoidespteronyssinus
Autore:
Wan, H; Winton, HL; Soeller, C; Taylor, GW; Gruenert, DC; Thompson, PJ; Cannell, MB; Stewart, GA; Garrod, DR; Robinson, C;
Indirizzi:
Univ London St Georges Hosp, Sch Med, Dept Pharmacol & Clin Pharmacol, London SW17 0RE, England Univ London St Georges Hosp London England SW17 0REon SW17 0RE, England Univ London Imperial Coll Sci Technol & Med, Sch Med, Clin Pharmacol Sect,London, England Univ London Imperial Coll Sci Technol & Med London England don, England Univ Calif San Francisco, Dept Lab Med, Cardiovasc Res Inst, Gene Therapy Core Ctr, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Western Australia, Queen Elizabeth II Med Ctr, Dept Med, Nedlands, WA6009, Australia Univ Western Australia Nedlands WA Australia 6009 ands, WA6009, Australia Univ Western Australia, Queen Elizabeth II Med Ctr, Dept Microbiol, Nedlands, WA 6009, Australia Univ Western Australia Nedlands WA Australia 6009 nds, WA 6009, Australia Univ Manchester, Sch Biol Sci, Manchester, Lancs, England Univ ManchesterManchester Lancs England Sci, Manchester, Lancs, England
Titolo Testata:
CLINICAL AND EXPERIMENTAL ALLERGY
fascicolo: 2, volume: 31, anno: 2001,
pagine: 279 - 294
SICI:
0954-7894(200102)31:2<279:TTPOOE>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
HOUSE-DUST MITE; DER-P-I; MEMBRANE-PROTEINS; ALLERGEN; PERMEABILITY; ASTHMA; CHILDHOOD; CLEAVAGE; RECEPTOR; DER-P-1;
Keywords:
asthma; house dust mite allergens; tight junctions; serine peptidases; adherens junctions; allergic sensitization; occludin; claudins;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Robinson, C Univ London St Georges Hosp, Sch Med, Dept Pharmacol & Clin Pharmacol, Cranmer Terrace, London SW17 0RE, England Univ London St Georges Hosp Cranmer Terrace London England SW17 0RE
Citazione:
H. Wan et al., "The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoidespteronyssinus", CLIN EXP AL, 31(2), 2001, pp. 279-294

Abstract

Background There have been only a few studies of how allergens cross the airway epithelium to cause allergic sensitization. House dust mite fecal pellets (HDMFP) contain several proteolytic enzymes. Group I allergens are cysteine peptidases, whilst those of groups 3, 6 and 9 have catalytic sites indicative of enzymes that mechanistically behave as serine peptidases. We have previously shown that the group 1 allergen Der p 1 leads to cleavage of tight junctions (TJs), allowing allergen delivery to antigen presenting cells. Objective In this study we determined whether HDMFP serine peptidases similarly compromise the airway epithelium by attacking TJs, desmosomes and adherens junctions. Methods Experiments were performed in monolayers of MDCK, Calu-3 or 16HBE14o-epithelial cells. Cell junction morphology was examined by 2-photon molecular excitation microscopy and digital image analysis. Barrier function was measured as mannitol permeability. Cleavage of cell adhesion proteins wasstudied by immunoblotting and mass spectrometry. Results HDMFP serine peptidases led to a progressive cleavage of TJs and increased epithelial permeability. Desmosomal puncta became more concentrated. Cleavage of TJs involved proteolysis of the TJ proteins, occludin and ZO-1. This was associated with activation of intracellular proteolysis of ZO-1. In contrast to occludin, E-cadherin of adherens junctions was cleaved less extensively. Although Calu-3 and 16HBE14o-cells expressed tethered ligand receptors for serine peptidases, these were not responsible for transducing the changes in TJs. Conclusion HDMFP serine peptidases cause cleavage of TJs. This study identifies a second general class of HDM peptidase capable of increasing epithelial permeability and thereby creating conditions that would favour transepithelial delivery of allergens.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 04:24:31