E-Selectin Early Overexpression Induced by Allogeneic Activation in Isolated Mouse Lung
| Autor: | Franck Joucher, Michèle German-Fattal, Guy-Michel Mazmanian |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
Vascular Cell Adhesion Molecule-1 Apoptosis Mice Necrosis E-selectin Cell Adhesion Animals Lymphocytes Cell adhesion Lung Protein Kinase C Mice Inbred C3H Transplantation biology Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Cell adhesion molecule Endothelial Cells Nuclear Proteins Interleukin CD58 Antigens Intercellular Adhesion Molecule-1 Intercellular adhesion molecule Molecular biology Sex-Determining Region Y Protein DNA-Binding Proteins Mice Inbred C57BL Endothelial stem cell Allogeneic Lymphocyte Immunology biology.protein Interleukin-2 Female Tumor necrosis factor alpha E-Selectin Transcription Factors |
| Zdroj: | Transplantation. 78:1283-1289 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/01.tp.0000137324.87116.41 |
| Popis: | Background The interaction between host lymphocytes and graft endothelial cells plays an important role in graft rejection. Methods Using our model of isolated ventilated lung from female mouse perfused with fresh blood from either isogeneic or allogeneic male mouse for 3 hours without noticeable ischemia, we have investigated the kinetics of the early events after endothelial cell triggering by E-selectin engagement. Results Isogeneic perfusion induced nonspecific endothelial cell activation, which was characterized by up-regulation of E-selectin, intercellular adhesion molecule (ICAM)-1, and of the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, and lymphotoxin-alpha (mRNAs by real-time polymerase chain reaction). Allogeneic perfusion was characterized after 3 hours by an additional loose adhesion of lymphocytes mediated by the E-selectin and related to the allogeneic activation of endothelial cells. These in turn expressed the I-A molecule (immunostaining). ICAM-1 and lymphocyte function-associated antigen (LFA)-3 mRNA levels were significantly increased in lung extracts after 2 hours, then vascular cell adhesion molecule (VCAM)-1 and TNF-alpha mRNAs after 3 hours without evidence of TNF-alpha production (enzyme-linked immunoadsorbent assay). The major participation of the E-selectin in early allogeneic activation by way of the protein kinase (PK)C pathway was confirmed by using a neutralizing anti-CD62E monoclonal antibody or the inhibitory PKC 19-31 fragment. Conclusions Altogether, our results demonstrate that E-selectin expression (1) is not a consequence of TNF-alpha triggering, (2) up-regulates its own expression and expression of I-A, VCAM-1, TNF-alpha, and lymphotoxin-alpha mRNAs, and (3) down-regulates expression of LFA-3 and ICAM-1 mRNAs. In conclusion, in our physiologic model, the E-selectin highly participates in the loose adhesion of allogeneic lymphocytes and in the early activation of endothelial cell and therefore in structural and functional lung alterations. |
| Databáze: | OpenAIRE |
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