Inflammatory responses to acute elevations of carbon dioxide in mice
Abstract
Health risks are described from elevated indoor air carbon dioxide (CO2), which often ranges from 1,000 to 4,000 ppm, but the mechanisms are unknown. Here, we demonstrate that mice exposed for 2 h to 2,000 or 4,000 ppm CO2exhibit, respectively, 3.4 ± 0.9-fold (SE, n = 6) and 4.1 ± 0.7-fold ( n = 10) elevations in circulating microparticles (MPs); neutrophil and platelet activation, and vascular leak in brain, muscle, and distal colon. Interleukin (IL)-1β content of MPs also increases after 2,000 ppm by 3.8 ± 0.6-fold ( n = 6) and after 4,000 ppm CO2by 9.3 ± 1.1-fold ( n = 10) greater than control. CO2–induced vascular damage is abrogated by treating mice with an antibody to IL-1β or an IL-1β receptor inhibitor. Injecting naïve mice with CO2-induced MPs expressing a protein found on mature neutrophils recapitulates vascular damage as seen with elevated CO2, and destruction of MPs in CO2-exposed mice abrogates vascular injuries without altering neutrophil or platelet activation. We conclude that environmentally relevant elevations of CO2trigger neutrophils to generate MPs containing high concentrations of IL-1β that cause diffuse inflammatory vascular injury.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 01, 2017
- Source ID
- 10.1152/japplphysiol.00343.2017
Entities
People
- Jingping Hu
- Ming Yang
- Stephen R. Thom
- Veena M. Bhopale
Organizations
- Office of Naval Research
- University of Maryland School of Medicine