CPPD Crystals

Calcium pyrophosphate dihydrate (CPPD) is the aetiological agent of the joint acute inflammatory disease pseudogout. Notably, research has demonstrated that CPPD crystals induce the release of interleukin (IL)-1β in response to the activation of the NLRP3 (also known as NALP3 or cryopyrin) inflammasome [1]. The NLRP3 inflammasome is an intracellular multi-protein complex that plays a central role in innate immunity [2, 3].

Mode of action:

Similar to uric acid, the causative agent of gout, CPPD crystals can act as endogenous danger signals that stimulate the innate immune system to produce inflammatory cytokines such as IL-1β [1]. CPPD crystals were shown to activate caspase-1, which is required for IL-1β maturation, through the NRLP3 (NALP3) inflammasome [2]. The NLRP3 inflammasome is a caspase-1-activating complex comprising the NLR protein NLRP3 and the adaptor ASC [3]. Engagement of the NRLP3 inflammasome is supported by the finding that macrophages from mice deficient in various components of the inflammasome do not respond to the injection of CPPD crystals [2].

Key features of CPPD crystals:

• Potent inducer of the NLRP3 inflammasome
• Each lot is functionally tested

Read our review on the NLRP3 inflammasome.

Download our Practical guide on Inflammasomes.

References:

1. Shi Y. et al., 2003. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425(6957):516-21
2. Martinon F. et al., 2006. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 440(7081):237-41.
3. Martinon F. & Tschopp J., 2004. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell. 117(5):561-74.