Complement Membrane Attack Complexes Assemble NLRP3 Inflammasomes Triggering IL-1 Activation of IFN-γ-Primed Human Endothelium.

ABSTRACT:

Rationale

Complement activation contributes to multiple immune-mediated pathologies. In late allograft failure, donor-specific antibody deposits complement membrane attack complexes (MAC) on graft endothelial cells (ECs), substantially increasing their immunogenicity without causing lysis. Internalized MAC stabilize NIK (NF-κB [nuclear factor kappa-light-chain-enhancer of activated B cells]-inducing kinase) protein on Rab5+MAC+ endosomes, activating noncanonical NF-κB signaling. However, the link to increased immunogenicity is unclear.

Objective

To identify mechanisms by which alloantibody and internalized MAC activate ECs to enhance their ability to increase T-cell responses.

Methods and results

In human EC cultures, internalized MAC also causes NLRP3 (NOD-like recep

SUBMITTER: Xie CB 

PROVIDER: S-EPMC6557295 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature