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Abstract: FR-PO219

Recognition of Apoptotic Cells by Viable Proximal Tubular Epithelial Cells (PTEC) Induces Death Receptor (DR)-Dependent PTEC Death: Dual Modes of PTEC Death Following Injury

Session Information

Category: Cell Biology

  • 202 Apoptosis, Proliferation, Autophagy, Cell Senescence, Cell Transformation


  • Dietrich, Michael E., University of Illinois at Chicago, Chicago, Illinois, United States
  • Feng, Lanfei, University of Illinois at Chicago, Chicago, Illinois, United States
  • Rauch, Joyce, McGill University, Montreal, Quebec, Canada
  • Levine, Jerrold S., University of Illinois at Chicago, Chicago, Illinois, United States

We have shown that mouse kidney PTEC have distinct non-competing receptors for apoptotic and necrotic targets. Recognition of apoptotic, but not necrotic, targets induces apoptotic death of PTEC responders. Here we study the role of DRs and their ligands (DR-L) in this process.


Responder cells were BU.MPT cells, a conditionally immortalized PTEC line. Target cells, induced to undergo apoptosis or necrosis, were homologous (BU.MPT) or heterologous (DO11.10 lymphocytes).


Apoptotic target-induced death of PTEC responders is profound (~100% by 48-72 h) and, at least in part, DR-dependent, as shown by caspase-8 activation and augmented survival upon caspase-8 inhibition. To evaluate the role of DRs, we compared expression of DR3, DR5, and Fas in PTEC responders, exposed to dead targets. Expression fell into one of two patterns: (1) DR3: Responders at rest (i.e., not exposed to targets) lacked DR expression. 18 h after exposure to apoptotic (but not necrotic) targets, ~50% of responders newly expressed DR3. (2) Fas and DR5: Responders at rest expressed Fas and DR5 constitutively. 18 h after exposure to apoptotic (but not necrotic) targets, ~50% of responders had undetectable Fas and DR5. We next examined DR-shifted responders (i.e, with new DR3 expression, or lost Fas and DR5 expression). Consistent with apoptosis induction following exposure to apoptotic (but not necrotic) targets, DR-shifted PTEC responders of both patterns were smaller in size and positive for caspase-3 activation. Notably, quiescent PTEC do not express DR-L. However, after exposure to apoptotic (but not necrotic) targets, PTEC produced and secreted FasL and TRAIL. Pharmacologic inhibition of FasL and TRAIL augmented survival of apoptotic target-exposed PTEC.


Exposure of viable PTEC to apoptotic (but not necrotic) targets induces PTEC apoptosis via DR-dependent mechanisms. Expression of Fas and DR5 is constitutive, while expression of their ligands, FasL and TRAIL, is induced by apoptotic target recognition. We hypothesize that PTEC injury is characterized by two distinct waves of cell death. In the 1st wave, PTEC death is the direct result of injury. In the 2nd wave, PTEC death is independent of injury, and the result of receptor-mediated recognition of dead or dying PTEC.