[Role of endothelial dysfunction in the development of severe sepsis--the pathomechanism, evaluation by laboratory tests and new therapeutic strategies].
Tumor necrosis factor (TNF) is critically involved in biological responses against various insults. TNF excessively produced by monocytes or macrophages activates endothelial cells and neutrophils, thereby inducing endothelial cell injury. Endothelial cells are capable of inhibiting TNF production by producing prostaglandins that inhibit TNF production. Sensory neurons play an important role in promotion of the endothelial production of prostaglandins by releasing calcitonin gene-related peptide. Neutrophils activated by TNF release a huge amount of neutrophil elastase that is capable of decreasing endothelial prostaglandin production. Consequently, TNF production is enhanced, leading to the development of multi-organ failure in sepsis. E-selectin, an endothelial leukocyte adhesion molecule, is released from the endothelial cell membrane by the action of TNF and exists as soluble E-selectin in plasma. The detection of increases in plasma levels of soluble E-selectin in patients with systemic inflammatory response syndrome predicts the imminent onset of acute respiratory syndrome. Early detection of increases in plasma levels of soluble E selectin by a rapid assay system, developed by the authors, enables early effective treatment of patients with sepsis.
Okajima
Kenji
K
Department of Translational Medical Science Research, Nagoya City University Graduate School of Medical Sciences, Nagoya.
Harada
Naoaki
N
Nakagawa
Takao
T
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D019040:E-Selectin / Q000097:blood* / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D009102:Multiple Organ Failure / Q000517:prevention & control; D011237:Predictive Value of Tests; D011453:Prostaglandins / Q000096:biosynthesis; D053491:Proteinase Inhibitory Proteins, Secretory / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome / Q000175:diagnosis / Q000517:prevention & control; D018805:Sepsis / Q000175:diagnosis* / Q000209:etiology* / Q000628:therapy; D012720:Severity of Illness Index; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000925:Anticoagulants; D015415:Biomarkers; D019040:E-Selectin; D004967:Estrogens; D011453:Prostaglandins; D053491:Proteinase Inhibitory Proteins, Secretory; D014409:Tumor Necrosis Factor-alpha