T Shibahara1, J N Wilcox, T Couse, J L Madara. 1. Department of Pathology and Laboratory Medicine, Division of Hematology/Oncology, Emory University, Atlanta, Georgia, USA.
Abstract
BACKGROUND & AIMS: Although homing of intraepithelial lymphocytes (IEL) into intestinal epithelia seems to be guided by signals from epithelia, little is known concerning functional epithelial-derived chemoattractants for IEL. METHODS: Epithelial chemoattractants for IEL were analyzed using chemotaxis chamber system, enzyme-linked immunosorbent assay, and in situ hybridization using human epithelial lines and IEL lines. RESULTS: Epithelial-conditioned media induced IEL chemotaxis, and this activity was markedly enhanced by prestimulation of epithelia with interferon-(IFN)-gamma. This chemotaxis (stimulation +) was significantly inhibited by neutralizing antibodies to IFN-gamma inducible protein-10 (IP-10) or to monokine induced by IFN-gamma (MIG). Furthermore, while high amounts of IP-10 and MIG were detected in epithelial-conditioned media after IFN-gamma stimulation, equivalent concentrations of recombinant IP-10 and MIG reproduced IEL chemotaxis. Production of IP-10 and MIG in fresh epithelial cells was supported by in situ hybridization and enzyme-linked immunosorbent assay. Lastly, fresh human IEL constitutively expressed CXCR-3 (the common receptor for IP-10 and MIG), and fresh IEL also exhibited chemotaxis to by rIP-10, rMIG, and epithelial-conditioned media. CONCLUSIONS: Epithelial cells produce chemoattractants for IEL, and such chemokine production is regulated by proinflammatory cytokines such as IFN-gamma. IP-10 and MIG may serve as potentially important epithelial chemokines for IEL, especially under inflammatory conditions.
BACKGROUND & AIMS: Although homing of intraepithelial lymphocytes (IEL) into intestinal epithelia seems to be guided by signals from epithelia, little is known concerning functional epithelial-derived chemoattractants for IEL. METHODS: Epithelial chemoattractants for IEL were analyzed using chemotaxis chamber system, enzyme-linked immunosorbent assay, and in situ hybridization using human epithelial lines and IEL lines. RESULTS: Epithelial-conditioned media induced IEL chemotaxis, and this activity was markedly enhanced by prestimulation of epithelia with interferon-(IFN)-gamma. This chemotaxis (stimulation +) was significantly inhibited by neutralizing antibodies to IFN-gamma inducible protein-10 (IP-10) or to monokine induced by IFN-gamma (MIG). Furthermore, while high amounts of IP-10 and MIG were detected in epithelial-conditioned media after IFN-gamma stimulation, equivalent concentrations of recombinant IP-10 and MIG reproduced IEL chemotaxis. Production of IP-10 and MIG in fresh epithelial cells was supported by in situ hybridization and enzyme-linked immunosorbent assay. Lastly, fresh human IEL constitutively expressed CXCR-3 (the common receptor for IP-10 and MIG), and fresh IEL also exhibited chemotaxis to by rIP-10, rMIG, and epithelial-conditioned media. CONCLUSIONS: Epithelial cells produce chemoattractants for IEL, and such chemokine production is regulated by proinflammatory cytokines such as IFN-gamma. IP-10 and MIG may serve as potentially important epithelial chemokines for IEL, especially under inflammatory conditions.
Authors: F Annunziato; L Cosmi; F Liotta; E Lazzeri; P Romagnani; R Angeli; L Lasagni; R Manetti; F Marra; C Gerard; I Petrai; P Dello Sbarba; F Tonelli; E Maggi; S Romagnani Journal: Gut Date: 2005-12-20 Impact factor: 23.059
Authors: Heuy-Ching Wang; Sara M Dann; Pablo C Okhuysen; Dorothy E Lewis; Cynthia L Chappell; Douglas G Adler; A Clinton White Journal: Infect Immun Date: 2006-10-16 Impact factor: 3.441