Inflammasome-Induced Osmotic Pressure and the Mechanical Mechanisms Underlying Astrocytic Swelling and Membrane Blebbing in Pyroptosis

Abstract

Cell swelling and membrane blebbing are characteristic of pyroptosis. In the present study, we explored the role of intracellular tension activity in the deformation of pyroptotic astrocytes. Protein nanoparticle-induced osmotic pressure (PN-OP) was found to be involved in cell swelling and membrane blebbing in pyroptotic astrocytes, and was associated closely with inflammasome production and cytoskeleton depolymerization. However, accumulation of protein nanoparticles seemed not to be absolutely required for pyroptotic permeabilization in response to cytoskeleton depolymerization. Gasdermin D activation was observed to be involved in modification of typical pyroptotic features through inflammasome-induced OP upregulation and calcium increment. Blockage of nonselective ion pores can inhibit permeabilization, but not inflammasome production and ion influx in pyroptotic astrocytes. The results suggested that the inflammasomes, as protein nanoparticles, are involved in PN-OP upregulation and control the typical features of pyroptotic astrocytes.

NLRP3/Caspase-1-Mediated Pyroptosis of Astrocytes Induced by Antipsychotics Is Inhibited by a Histamine H1 Receptor-Selective Agonist

“…Astrocyte pyroptosis involves cell swelling, pore formation in the cell membrane and increased membrane permeabilization ( Chen et al, 2016 ; Zheng et al, 2021 ). The present study found that FMPH high dose co-treatment significantly inhibited olanzapine-, quetiapine-, risperidone-, or haloperidol-induced increased expression of NLRP3, caspase-1, GSDMD and IL-1β.…”

“…However, the exact mechanism by which antipsychotics induce pore formation is unknown. A recent study in astrocytes reported that activated GSDMD increased osmotic pressure (OP) and intracellular calcium, and these effects contributed to astrocyte swelling and membrane blebbing ( Zheng et al, 2021 ). Additional studies that investigate the effects of antipsychotics on OP and calcium flux and whether these effects are related to GSDMD are warranted.…”

“…The effects of antipsychotics and FMPH treatment on cell morphological changes were investigated based on previous studies ( Chen et al, 2016 ; Zheng et al, 2021 ). In brief, 1 × 10 5 cells/well were seeded on glass coverslips placed in six-well plates.…”

Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome

“…1 F). In addition, IF tension is closely associated with OP alteration [ 13 , 14 , 38 ], and JK and Tax co-treatment could partly improve IF tension caused by AngII, while JK, Tax, or both had no effect on the BK model (Fig. 1 G).…”

“…Water metabolism and edema occurrence depend on transmembrane oncotic pressure gradients in the body [ 13 ]. Based on a recent study, protein nanoparticle production can result in increased osmotic pressure (PN-OP) and water flow, which is also thought to involve upregulation of membrane fluidity and promotes nonselective permeability [ 14 , 15 ]. Previous studies suggested that ARDS is associated with the secretion of proinflammatory cytokines and inflammasome production [ 1 , 16 , 17 ].…”