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Editorial
. 2022 Sep 1;206(5):532-534.
doi: 10.1164/rccm.202205-0977ED.

Misbehaving Guests in the Right Ventricle: Macrophage-NLRP3 Activation in Pulmonary Hypertension

Rafael Sobrano Fais  1 , Tim Lahm  1   2   3
Affiliations
Editorial

Misbehaving Guests in the Right Ventricle: Macrophage-NLRP3 Activation in Pulmonary Hypertension

Rafael Sobrano Fais et al. Am J Respir Crit Care Med. .
No abstract available

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Figures

Figure 1.
Figure 1.
Overview of the NLRP3 (nucleotide-binding domain, leucine-rich–containing family, and pyrin domain-containing protein 3) inflammasome signaling pathway. NLRP3 inflammasome signaling consists of three major steps. In the priming step, DAMPs, such as HMGB1 (high mobility group box protein 1) or IL-1β, as well as PAMPs, such as LPS, interact with cell membrane receptors such as TLR4 (Toll-like receptor 4), IL-1R (IL-1 receptor), or IL-6R to activate the transcription factor NF-κB (nuclear factor κB). NF-κB then translocates to the nucleus to increase transcription of the inflammasome components NLRP3, ASC (apoptosis-associated speck-like protein containing an caspase recruitment domain), and procaspase 1, as well as the effector precursors, pro–IL-1β and pro–IL-18. In the activation step, the NLRP3 inflammasome is activated by factors such as extracellular ATP, bacterial pore-forming toxins, or mitochondrial reactive oxygen species (ROS). Potassium efflux and calcium influx are also involved in this step. On activation, NLRP3 recruits and forms a complex with ASC as well as procaspase 1. In the final step, the assembled inflammasome platform cleaves pro–IL-1β and pro–IL-18 to activate IL-1β and IL-18, respectively. The NLRP3 inflammasome also activates the pore-forming protein GSDMD (gasdermin D), resulting in membrane pore formation, cytokine release, and, ultimately, pyroptosis. This pathway is best described in immune cells but has also been identified in nonimmune cells. DAMPs = danger-associated molecular patterns; PAMPs = pathogen-associated molecular patterns.
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References

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