[Regulation of inflammatory responses by endothelial cells--understanding the molecular mechanism(s) and its therapeutic application to sepsis].
Endothelial cells are activated by shear-stress and inflammatory mediators that are capable of activating sensory neurons. Activated endothelial cells increase the production of nitric oxide and prostaglandins, thereby regulating inflammatory responses induced by various insults. Dysfunction of sensory neurons and excess inflammatory mediators released from activated neutrophils damage endothelial cells, thereby increasing inflammatory responses such as an increase in tumor necrosis factor production. Pulmonary endothelial dysfunction plays a critical role in the development of acute lung injury and shock, leading to multi-organ failure. Determination of soluble E-selectin in serum samples of patients with sepsis predicts the future development of acute lung injury. Therapeutic agents that are capable of stimulating sensory neurons or inhibiting leukocyte activation might be useful in the treatment of severe sepsis especially when these agents are administered in the early stage of severe sepsis.
Okajima
Kenji
K
Department of Translational Medical Science Research, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601.
D000818:Animals; D001696:Biomechanical Phenomena; D042783:Endothelial Cells / Q000502:physiology*; D011464:Epoprostenol; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D018836:Inflammation Mediators; D007334:Insulin-Like Growth Factor I; D019272:Leukocyte Elastase; D009475:Neurons, Afferent / Q000502:physiology; D009569:Nitric Oxide; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology*; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha
D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D011464:Epoprostenol; D019272:Leukocyte Elastase