Osteoclast exosomes pre-stimulate pulmonary endothelial cells to aggravate sepsis-induced acute lung injury

Abstract

Micro-vascular hyperpermeability is often induced by the extensive burns and subsequent sepsis, and the most common clinical complication is acute lung injury (ALI), which is mortal and is the focus of our attention when treating large-area burns. We found that elderly patients have increased lung vascular permeability after extensive burns and the incidence of ALI is heavier than that of young people, which may be related to multiple underlying diseases in the elderly. Interestingly, some female patients who have total ovariectomy in the past also suffered more severe pulmonary vascular endothelial injury and ALI after extensive burns. So simple osteoporosis might have direct relationship with lung microvascular barrier disruption and the development of ALI under sepsis. In the clinic work, we found that Osteoporosis might exacerbate the lung edema after extensive burns. Additionally, by establishing the mice osteoporosis model and performing LPS in vivo to induce the sepsis-associated ALI model, we found that sepsis induced more severe ALI in the osteoporosis mice. Thus, we hypothesized that osteoporosis-mediated osteoclast activation might pre-stimulated pulmonary micro-endothelium and aggravate sepsis-induced endothelial injury and ALI by osteoclast exosomes.