Plasma gelsolin modulates the production and fate of IL-1β-containing microparticles following high-pressure exposure and decompression.

Veena M Bhopale, Deepa Ruhela, Kaighley D Brett, Nathan Z Nugent, Noelle K Fraser, Susan L Levinson, Mark J DiNubile, Stephen R Thom

Journal of applied physiology (Bethesda, Md. : 1985) 2021 May 01

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Plasma gelsolin (pGSN) levels fall in association with diverse inflammatory conditions. We hypothesized that pGSN would decrease due to the stresses imposed by high pressure and subsequent decompression, and repletion would ameliorate injuries in a murine decompression sickness (DCS) model. Research subjects were found to exhibit a modest decrease in pGSN level while at high pressure and a profound decrease after decompression. Changes occurred concurrent with elevations of circulating microparticles (MPs) carrying interleukin (IL)-1β. Mice exhibited a comparable decrease in pGSN after decompression along with elevations of MPs carrying IL-1β. Infusion of recombinant human (rhu)-pGSN into mice before or after pressure exposure abrogated these changes and prevented capillary leak in brain and skeletal muscle. Human and murine MPs generated under high pressure exhibited surface filamentous actin (F-actin) to which pGSN binds, leading to particle lysis. In addition, human neutrophils exposed to high air pressure exhibit an increase in surface F-actin that is diminished by rhu-pGSN resulting in inhibition of MP production. Administration of rhu-pGSN may have benefit as prophylaxis or treatment for DCS.NEW & NOTEWORTHY Inflammatory microparticles released in response to high pressure and decompression express surface filamentous actin. Infusion of recombinant human plasma gelsolin lyses these particles in decompressed mice and ameliorates particle-associated vascular damage. Human neutrophils also respond to high pressure with an increase in surface filamentous actin and microparticle production, and these events are inhibited by plasma gelsolin. Gelsolin infusion may have benefit as prophylaxis or treatment for decompression sickness.

Citation

Veena M Bhopale, Deepa Ruhela, Kaighley D Brett, Nathan Z Nugent, Noelle K Fraser, Susan L Levinson, Mark J DiNubile, Stephen R Thom. Plasma gelsolin modulates the production and fate of IL-1β-containing microparticles following high-pressure exposure and decompression. Journal of applied physiology (Bethesda, Md. : 1985). 2021 May 01;130(5):1604-1613