Premium
Deposition of microparticles by neutrophils onto inflamed epithelium: a new mechanism to disrupt epithelial intercellular adhesions and promote transepithelial migration
Author(s) -
ButinIsraeli Veronika,
Houser Madelyn C.,
Feng Mingli,
Thorp Edward B.,
Nusrat Asma,
Parkos Charles A.,
Sumagin Ronen
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600734r
Subject(s) - epithelium , intracellular , intestinal epithelium , microbiology and biotechnology , chemistry , inflammation , tight junction , cell junction , chemokine , immunology , biology , cell , pathology , biochemistry , medicine
Neutrophil [polymorphonuclear leukocyte (PMN)] transepithelial migration (TEM) is a hallmark of inflammatory mucosal disorders. PMN TEM is associated with epithelial injury; however, mechanisms involved in this process are not well defined. The current work describes a new mechanism whereby deposition of PMN membranederived microparticles (PMN‐MPs) onto intestinal epithelial cells (IECs) during TEM leads to loss of epithelial cadherins, thus promoting epithelial injury and increased PMN recruitment. PMN‐MPs secreted by activated PMNs during TEM displayed a high level of enzymatically activematrixmetalloproteinase 9 (MMP‐9), and were capable of mediating potent effects on IEC integrity. Isolated PMN‐MPs efficiently bound to IEC monolayers and induced cleavage of desmoglein‐2 (DSG‐2) but not E‐cadherin, leading to disruption of IEC intercellular adhesions. Furthermore, PMN‐MP binding to intestinal epithelium in vitro in transwell assays and in vivo in ligated intestinal loop preparations facilitated increases in PMN TEM. These effects were MMP‐9 dependent and were reversed in the presence of specific pharmacological inhibitors. Finally, we demonstrated that IEC Dsg‐2 serves as a barrier for migrating PMNs, and its removal by PMN‐MP‐associated MMP‐9 facilitates PMNtrafficking across epithelial layers. Our findings thus implicate PMN‐MPs in PMN‐mediated inflammation and epithelial damage, as observed in inflammatory disorders ofmucosal surfaces.—Butin‐Israeli, V., Houser, M.C., Feng, M., Thorp, E. B., Nusrat, A., Parkos, C. A, Sumagin, R. Deposition of microparticles by neutrophils onto inflamed epithelium: anewmechanism to disrupt epithelial intercellular adhesions and promote transepithelialmigration. FASEB J. 30, 4007–4020 (2016). www.fasebj.org