Related Experiment Video
Updated: Sep 30, 2025
Pre-clinical Model of Cardiac Donation after Circulatory Death
Published on: August 2, 2019
CD14 blockade to prevent ischemic injury to donor organs
Jason Own1, Richard Ulevitch2, Dianne McKay3
1Department of Immunology and Microbiology, Scripps Research Institute, 10466 North Torrey Pines Rd, La Jolla, CA 92037, United States of America; Yale College, PO Box 208241, New Haven, CT 06520-8241, United States of America.
Abstract:
The purpose of this review is to highlight the potential role for the cluster of differentiation protein 14 (CD14), a co-receptor for toll-like receptor (TLR) signals and as a proximal target for innate immune signals induced during procurement of solid organs for transplantation. CD14 facilitates the detection of multiple pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) by various TLRs. All solid organs used for transplantation are exposed to PAMPs and DAMPs generated during the course of procurement that inevitably trigger injurious inflammatory responses in the donor organ. Multiple experimental animal studies and observations in human organs have provided a solid rationale to consider CD14 blockade as a therapeutic target. CD14 has been recognized for over three decades to play an essential role in innate immune signals associated with sepsis. More recent data now show that genetic deletion or antibody blockade of CD14 can modify ischemic tissue injury in the kidney, liver, heart and lung. Thus, data presented in this review suggest that anti-CD14 directed therapies might be applied to organ preservation strategies in solid organ transplantation.
Insights
Cluster of differentiation protein 14 (CD14) plays a key role in organ transplant inflammation. Blocking CD14 may improve organ preservation strategies and reduce tissue injury during transplantation.
Area of Science:
- Immunology
- Transplantation Biology
- Molecular Medicine
Background:
- Cluster of differentiation protein 14 (CD14) is a co-receptor for toll-like receptor (TLR) signaling.
- CD14 detects pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), crucial in innate immunity.
- Solid organ procurement exposes organs to PAMPs and DAMPs, initiating inflammatory responses.
Purpose of the Study:
- To review the role of CD14 in innate immune responses during solid organ transplantation.
- To highlight CD14 as a potential therapeutic target for modulating inflammatory responses in transplanted organs.
Main Methods:
- Review of experimental animal studies and human organ observations.
- Analysis of data on CD14's role in sepsis and ischemic tissue injury.
- Exploration of CD14 blockade as a therapeutic strategy.
Main Results:
- CD14 blockade has shown potential in modifying ischemic tissue injury in kidneys, liver, heart, and lungs.
- Genetic deletion or antibody blockade of CD14 can mitigate inflammatory responses.
- CD14 is implicated in innate immune signaling relevant to transplantation.
Conclusions:
- CD14 blockade represents a promising therapeutic target for organ preservation.
- Anti-CD14 therapies may enhance strategies for solid organ transplantation.
- Targeting CD14 could reduce inflammatory damage in donor organs.
