Hemozoin

Inflammasome activation with Hemozoin crystals

NLRP3 Inflammasome Inducer - Synthetic heme crystal

Hemozoin (HZ) is a dark-brown crystallized heme byproduct generated by the intraerythrocytic parasite Plasmodium falciparum, the causative agent of malaria. It is taken up by macrophages initiating signals that lead to the production of interleukin (IL)-1β and IL-18.  The hemozoin-induced production of these pro-inflammatory cytokines is dependent on the activation of the NLRP3 inflammasome [1,2].

 More details

Synthetic HZ has been shown to possess adjuvant properties that differ depending on the method of synthesis [3]. InvivoGen provides a chemically synthesized HZ using an acidic method. The biological activity of HZ has been validated using InvivoGen's HEK-Blue™ IL-1β cells and THP1-Null2 cell.

Key features:

• 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. Shio MT. et al., 2009. Malarial hemozoin activates the NLRP3 inflammasome through Lyn and Syk kinases. PLoS Pathog. 5(8):e1000559.
2. Dostert C. et al., 2009. Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS One. 4(8):e6510.
3. Coban C. et al., 2010. The malarial metabolite hemozoin and its potential use as a vaccine adjuvant. Allergol Int. 59(2):115-24.

Figures

Mature IL-1β production in THP1-Null2 cells. Human THP-1 monocytes were primed for 3 hours with LPS-EK(10 µg/ml) prior to the incubation with increasing concentrations of Hemozoin (HZ). The next day, the supernatant was incubated with HEK-Blue™ IL-1β cells for 24 hours and IL-1β was assessed using QUANTI-Blue™ Solution. The optical density (OD) was read at 630 nm.

Specifications

Working concentration: 50 - 400 µg/ml
CAS number: 39404-00-7

Solubility: Insoluble. Rehydration of hemozoin with water or saline results in a dark brown suspension.

Quality control:

• The biological activity has been validated using cellular assays.
• The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.

Contents

Hemozoin is provided as solid dark-green to black crystals.

• 5 mg Hemozoin

Hemozoin is shipped at room temperature.

Store at -20°C

Details

The NLRP3 inflammasome is an intracellular multi-protein complex that plays a central role in innate immunity. It is activated by a two-step process. A first signal (‘priming’) is provided by pathogen-associated molecular patterns (PAMPs) or cytokines. It allows the transcriptional upregulation of key inflammasome actors and the post-translational modification of NLRP3 . The second signal (‘activation’) is provided by a wide array of stimuli including microbial toxins, endogenous molecules or crystalline substances. The current paradigm is that NLRP3 does not bind directly to these molecules. Rather it senses downstream cytosolic stress signals such as K+ efflux. This  triggers inflammasome multimerization and pro-caspase-1 maturation. Proximity-induced autolytic activation of caspase-1 leads to the formation of gasdermin D (GSDMD) pores at the cell surface, allowing IL-1β/IL-18 and alarmin secretion, and ultimately, pyroptosis [1,2].

References:

1. Swanson K.V. et al., 2019. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 19:477.
2. Groslambert M. & Py B. 2018. Spotlight on the NLRP3 inflammasome pathway. J. Inflamm. Res. 11:359.