Related Experiment Video
Updated: May 28, 2026

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
Published on: May 3, 2024
Ripped to death
Ricardo Weinlich1, Christopher P Dillon, Douglas R Green
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Abstract:
An old puzzle in the field of cell death was solved recently: the mysterious embryonic lethality of animals deficient in caspase-8 or Fas-associated death domain (FADD), proteins involved in a pathway of apoptosis. This lethality is caused by a failure to develop the yolk sac vasculature rather than a lack of apoptosis. Remarkably, development is rescued by ablation of either of two receptor interacting serine-threonine kinases (RIPKs). Despite being well known cell killers, caspase-8 and FADD act together to block RIPK-mediated necrosis. To manifest this newly elucidated pro-survival function, FADD and caspase-8 depend on FLIP(Long), a catalytically inactive caspase-8 homolog. In this review, the mechanism by which RIPK necrotic death is inhibited by this trio is discussed, as well as how RIPKs might themselves mediate cell death.
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