Synthetic fibronectin peptides interrupt inflammatory cell infiltration in transforming growth factor beta 1 knockout mice
| Autor: | Hongsheng Tian, Marielle Christ, Leo T. Furcht, Sharon M. Wahl, Keith L. Hines, Ashok B. Kulkarni, Stefan Karlsson, James B. McCarthy, Nancy McCartney-Francis, Jerrold M. Ward |
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| Rok vydání: | 1994 |
| Předmět: |
Molecular Sequence Data
Cell Fluorescent Antibody Technique Spleen Gene mutation Extracellular matrix Mice Transforming Growth Factor beta Cell Adhesion medicine Animals Amino Acid Sequence Cell adhesion Cells Cultured Mice Knockout Multidisciplinary biology Transforming growth factor beta medicine.disease Molecular biology Fibronectins Fibronectin Chemotaxis Leukocyte medicine.anatomical_structure Leukocytes Mononuclear biology.protein Endothelium Vascular Infiltration (medical) Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 91:5187-5191 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.91.11.5187 |
| Popis: | Pronounced mononuclear leukocyte (MNL) infiltration occurs in multiple organs of mice homozygous for a transforming growth factor beta 1 (TGF-beta 1) loss-of-function gene mutation [TGF-beta 1 (-/-)], followed by cachexia and eventually death. Consistent with the increased leukocyte adhesion and tissue infiltration, MNLs isolated from spleen, thymus, and peripheral blood of symptomatic TGF-beta 1 (-/-) mice, as compared to littermate controls, exhibited increased adhesion to extracellular matrix proteins and to endothelial cells in vitro. Incubation of TGF-beta 1 (-/-) MNLs with selected synthetic peptides corresponding to cell- and heparin-binding sequences of fibronectin (FN) significantly attenuated adhesion of these cells not only to FN but also to endothelial cells in vitro. Based on these observations, mice were treated with the FN peptides in an attempt to rescue them from tissue inflammation and cardiopulmonary failure. Daily injections of a combination of four synthetic FN peptides that interact with beta 1-integrins and/or cell surface proteoglycans blocked the massive infiltration of MNLs into the heart and lungs of TGF-beta 1 (-/-) mice. Peptide treatment initiated on day 8, coincident with the first evidence of increased leukocyte-endothelial cell interactions, not only blocked tissue infiltration but also moderated the lethal wasting syndrome. |
| Databáze: | OpenAIRE |
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