Sepsis is an illness in which the body has a severe reaction to a bacterial infection. Bacterial toxins activate the immune system, causing widespread inflammation and increased blood calcium levels, oxidative stress, and inflammatory factors. This increased inflammation and immune activation can cause fatal organ damage, particularly in the lungs. Gandhirajan and colleagues identified a signaling pathway that mediates lung injury during sepsis. Treatment with a calcium channel blocker known as BTP2 halted sepsis-induced lung injury in mice. In the image above, Gandhirajan and colleagues used 2-photon imaging to examine the pulmonary vasculature in mice (image is false colored).
During sepsis, acute lung injury (ALI) results from activation of innate immune cells and endothelial cells by endotoxins, leading to systemic inflammation through proinflammatory cytokine overproduction, oxidative stress, and intracellular Ca2+ overload. Despite considerable investigation, the underlying molecular mechanism(s) leading to LPS-induced ALI remain elusive. To determine whether stromal interaction molecule 1–dependent (STIM1-dependent) signaling drives endothelial dysfunction in response to LPS, we investigated oxidative and STIM1 signaling of EC-specific
Rajesh Kumar Gandhirajan, Shu Meng, Harish C. Chandramoorthy, Karthik Mallilankaraman, Salvatore Mancarella, Hui Gao, Roshanak Razmpour, Xiao-Feng Yang, Steven R. Houser, Ju Chen, Walter J. Koch, Hong Wang, Jonathan Soboloff, Donald L. Gill, Muniswamy Madesh