Published April 22, 2021 - More info
High mortality in acute lung injury (ALI) results from sustained proinflammatory signaling by alveolar receptors, such as TNF-α receptor type 1 (TNFR1). Factors that determine the sustained signaling are not known. Unexpectedly, optical imaging of live alveoli revealed a major TNF-α–induced surge of alveolar TNFR1 due to a Ca2+-dependent mechanism that decreased the cortical actin fence. Mouse mortality due to inhaled LPS was associated with cofilin activation, actin loss, and the TNFR1 surge. The constitutively active form of the GTPase, Rac1 (V12Rac1), given intranasally (i.n.) as a noncovalent construct with a cell-permeable peptide, enhanced alveolar filamentous actin (F-actin) and blocked the TNFR1 surge. V12Rac1 also protected against ALI-induced mortality resulting from i.n. instillation of LPS or of Pseudomonas aeruginosa. We propose a potentially new therapeutic paradigm in which actin enhancement by exogenous Rac1 strengthens the alveolar actin fence, protecting against proinflammatory receptor hyperexpression, and therefore blocking ALI.
Galina A. Gusarova, Shonit R. Das, Mohammad N. Islam, Kristin Westphalen, Guangchun Jin, Igor O. Shmarakov, Li Li, Sunita Bhattacharya, Jahar Bhattacharya
Original citation: JCI Insight. 2021;6(6):e135753. https://doi.org/10.1172/jci.insight.135753
Citation for this corrigendum: JCI Insight. 2021;6(8):e150137. https://doi.org/10.1172/jci.insight.150137
During the preparation of this manuscript, the center panel of the bottom row of Figure 2D was inadvertently duplicated from the left panel of the bottom row of Figure 2D. The figure has been corrected.
The authors regret the error.
See the related article at Actin fence therapy with exogenous V12Rac1 protects against acute lung injury.