This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Epithelial cells form the body's frontline barriers, helping keep microbes, toxins and other harmful substances out. Yet these protective cells are constantly exposed to threats, including microbial infections.
Some bacteria produce pore-forming toxins that can oligomerize and act like microscopic drills, perforating the cell's plasma membrane. If these pores are not repaired quickly, cells can lose vital contents, suffer internal damage and eventually die. Understanding how epithelial cells rapidly repair toxin-induced membrane injuries is therefore important for understanding how tissues withstand bacterial attacks.
To investigate how cells respond to this damage, researchers Dr. Kazuko Saeki and professor Takehiko Yokomizo at Juntendo University focused on a signaling system involving 12-HHT, a bioactive lipid mediator, and BLT2, a receptor found primarily on epithelial cells. They investigated how lipid mediator signaling promotes plasma membrane repair and protects cells from membrane-damaging insults.
The study is published online in the Journal of Cell Biology. The researchers used human lung epithelial cells, canine kidney epithelial cells and primary mouse skin epidermal keratinocytes, comparing cells with natural, increased or absent BLT2 expression. They induced membrane damage using pneumolysin, streptolysin O, α-hemolysin or digitonin and assessed membrane injury, leakage and cell survival through microscopy, fluorescent dyes to assess membrane integrity, LDH-release assays and viability tests.
Electron microscopy was used to examine cells and extracellular vesicles. To investigate the mechanism, the team tested calcium-free conditions, measured 12-HHT levels by liquid chromatography–mass spectrometry and used inhibitors targeting BLT2, Rac1, actin polymerization, acid sphingomyelinase and 12-HHT production. They found that BLT2 helps epithelial cells survive after their membranes are damaged.
Under these conditions, cells with enhanced BLT2 signaling showed less membrane leakage, less visible damage, better mitochondrial health and higher survival rates. In contrast, cells lacking BLT2 were more likely to rupture and die. BLT2's benefit was seen with all the tested toxins as well as with digitonin, suggesting that it is part of a general membrane-repair system.
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