| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-40 |
Sentence |
denotes |
CCL5-CCR5-mediated apoptosis in T cells: |
| T2 |
41-104 |
Sentence |
denotes |
Requirement for glycosaminoglycan binding and CCL5 aggregation. |
| T3 |
105-256 |
Sentence |
denotes |
CCL5 (RANTES (regulated on activation normal T cell expressed and secreted)) and its cognate receptor, CCR5, have been implicated in T cell activation. |
| T4 |
257-423 |
Sentence |
denotes |
CCL5 binding to glycosaminoglycans (GAGs) on the cell surface or in extracellular matrix sequesters CCL5, thereby immobilizing CCL5 to provide the directional signal. |
| T5 |
424-590 |
Sentence |
denotes |
In two CCR5-expressing human T cell lines, PM1.CCR5 and MOLT4.CCR5, and in human peripheral blood-derived T cells, micromolar concentrations of CCL5 induce apoptosis. |
| T6 |
591-747 |
Sentence |
denotes |
CCL5-induced cell death involves the cytosolic release of cytochrome c, the activation of caspase-9 and caspase-3, and poly(ADP-ribose) polymerase cleavage. |
| T7 |
748-888 |
Sentence |
denotes |
CCL5-induced apoptosis is CCR5-dependent, since native PM1 and MOLT4 cells lacking CCR5 expression are resistant to CCL5-induced cell death. |
| T8 |
889-1077 |
Sentence |
denotes |
Furthermore, we implicate tyrosine 339 as a critical residue involved in CCL5-induced apoptosis, since PM1 cells expressing a tyrosine mutant receptor, CCR5Y339F, do not undergo apoptosis. |
| T9 |
1078-1161 |
Sentence |
denotes |
We show that CCL5-CCR5-mediated apoptosis is dependent on cell surface GAG binding. |
| T10 |
1162-1289 |
Sentence |
denotes |
The addition of exogenous heparin and chondroitin sulfate and GAG digestion from the cell surface protect cells from apoptosis. |
| T11 |
1290-1372 |
Sentence |
denotes |
Moreover, the non-GAG binding variant, (44AANA47)-CCL5, fails to induce apoptosis. |
| T12 |
1373-1564 |
Sentence |
denotes |
To address the role of aggregation in CCL5-mediated apoptosis, nonaggregating CCL5 mutant E66S, which forms dimers, and E26A, which form tetramers at micromolar concentrations, were utilized. |
| T13 |
1565-1737 |
Sentence |
denotes |
Unlike native CCL5, the E66S mutant fails to induce apoptosis, suggesting that tetramers are the minimal higher ordered CCL5 aggregates required for CCL5-induced apoptosis. |
| T14 |
1738-1918 |
Sentence |
denotes |
Viewed altogether, these data suggest that CCL5-GAG binding and CCL5 aggregation are important for CCL5 activity in T cells, specifically in the context of CCR5-mediated apoptosis. |