Augmentation of RANTES-induced extracellular signal-regulated kinase mediated signaling and T cell adhesion by elastase-treated fibronectin.
T cells migrating across extracellular matrix (ECM) barriers toward their target, the inflammatory site, should respond to chemoattractant cytokines and to the degradation of ECM by specific enzymes. In this study, we examined the effects of RANTES and ECM proteins treated with human leukocyte elastase on T cell activation and adhesion to the ECM. We found that human peripheral blood T cells briefly suspended with RANTES (0.1-100 ng/ml) had increased phosphorylation of their intracellular extracellular signal-regulated kinase (ERK), a mitogen-activated protein kinase involved in the activation of several intracellular downstream effector molecules implicated in cell adhesion and migration. Consequently, a small portion (12-20%) of the responding cells adhered to fibronectin (FN). However, when the T cells were exposed to RANTES in the presence of native immobilized FN, laminin, or collagen type I, ERK phosphorylation was partially inhibited, suggesting that this form of the ECM proteins can down-regulate RANTES-induced intracellular signaling. In contrast, when the T cells were exposed to RANTES in the presence of elastase-treated immobilized FN, but not to elastase-treated laminin, ERK phosphorylation was markedly increased. Furthermore, a large percentage (30%) of RANTES-activated T cells adhered to the enzymatically treated FN in a beta1 integrin-dependent fashion. Thus, while migrating along chemotactic gradients within the ECM, T cells can adapt their adhesive performance according to the level of cleavage induced by enzymes to the matrix.
Brill
A
A
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Hershkoviz
R
R
Vaday
G G
GG
Chowers
Y
Y
Lider
O
O
D000276:Adjuvants, Immunologic / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000502:physiology*; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D004790:Enzyme Induction / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D010196:Pancreatic Elastase / Q000494:pharmacology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology / Q000502:physiology*
D000276:Adjuvants, Immunologic; D018946:Chemokine CCL5; D005353:Fibronectins; D007797:Laminin; D003094:Collagen; D020928:Mitogen-Activated Protein Kinases; D010196:Pancreatic Elastase