title: A lymphocyte serine protease granzyme A causes detachment of a small-intestinal epithelial cell line (IEC-6).
abstract: Granzyme A (GzmA) is a serine protease (trypsin-like specificity) produced in cytotoxic lymphocytes. This enzyme is believed to enter virus-infected cells and growing tumors and induce apoptosis, but the roles of GzmA expressed in lymphocytes scattered through the epithelial layer of the normal small intestine are unknown. In the present study, recombinant rat GzmA (rGzmA) was found to cause morphological changes and detachment of a non-transformed rat small-intestinal epithelial cell line IEC-6, although the rGzmA-treated cells detached as aggregates with no changes characteristic of apoptosis. rGzmA-induced deformation and detachment occurred in IEC-6 cells plated with collagen type IV and fibronectin, but not in those plated with laminin. These findings suggest that GzmA in the normal small intestine participates in the reduction of adhesion between epithelial cells and basement membranes, through its ability to cleave extracellular matrix components.
authors.affiliation: Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hirayasu
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsuzuki
authors.forename: Tohru
authors.initials: T
authors.lastname: Fushiki
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D024141:Collagen Type IV / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000032:analysis; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D053804:Granzymes / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D007421:Intestine, Small / Q000166:cytology*; D007797:Laminin / Q000378:metabolism; D008214:Lymphocytes / Q000201:enzymology*; D010843:Pichia / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
chemical_list: D024141:Collagen Type IV; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D011994:Recombinant Proteins; D053804:Granzymes