Hashiguchi N, Ogura H, Tanaka H, Koh T, Nakamori Y, Noborio M, Shiozaki T, Nishino M, Kuwagata Y, Shimazu T, Sugimoto H
Department of Traumatology, Osaka University Medical School, Suita-shi, Osaka, Japan.
J Trauma. 2001 Dec;51(6):1104-9. doi: 10.1097/00005373-200112000-00015.
Heat shock proteins (HSPs) in cells, as molecular chaperons, have been reported to regulate cell functions. The objective of this study was to investigate the HSP expression in polymorphonuclear leukocytes (PMNLs) from severe septic patients and the relation between the expression of HSPs and PMNL function.
In blood samples from 21 patients with sepsis and serum C-reactive protein levels more than 10 mg/dL, we used flow cytometry to measure expressions of HSP27, HSP60, HSP70, and HSP90; oxidative activity; and levels of apoptosis in PMNLs during sepsis. In in vitro studies, we used cells from 14 healthy volunteers to examine the relation between the expression of HSP70 and PMNL function. Quercetin (30 microM), a suppressor of HSP, and sodium arsenite (100 microM), an inducer of HSP, were used to regulate the expression of HSP70 in PMNLs, and oxidative activity and apoptosis in these cells were measured.
In patients with sepsis, the expressions of HSP27, HSP60, HSP70, and HSP90 and oxidative activity in PMNLs were significantly increased. Apoptosis of these PMNLs was markedly inhibited. In the in vitro studies, administration of sodium arsenite enhanced the expression of HSP70, significantly increased oxidative activity, and inhibited apoptosis. Administration of quercetin before sodium arsenite prevented the expression of HSP70, the increase in oxidative activity, and the inhibition of apoptosis.
Sepsis causes the enhanced expression of HSPs in activated PMNLs. In PMNLs with enhanced expression of HSP70, oxidative activity is increased and apoptosis is inhibited. The enhanced expression of HSPs may play a role in regulating PMNL function in patients with sepsis.
细胞中的热休克蛋白（HSPs）作为分子伴侣，据报道可调节细胞功能。本研究的目的是调查重症脓毒症患者多形核白细胞（PMNLs）中HSP的表达情况以及HSPs表达与PMNL功能之间的关系。
在21例脓毒症患者且血清C反应蛋白水平超过10mg/dL的血样中，我们使用流式细胞术测量脓毒症期间PMNLs中HSP27、HSP60、HSP70和HSP90的表达、氧化活性及凋亡水平。在体外研究中，我们使用14名健康志愿者的细胞来检测HSP70表达与PMNL功能之间的关系。使用HSP抑制剂槲皮素（30μM）和HSP诱导剂亚砷酸钠（100μM）来调节PMNLs中HSP70的表达，并测量这些细胞中的氧化活性和凋亡情况。
脓毒症患者中，PMNLs中HSP27、HSP60、HSP70和HSP90的表达及氧化活性显著增加。这些PMNLs的凋亡受到明显抑制。在体外研究中，给予亚砷酸钠可增强HSP70的表达，显著增加氧化活性并抑制凋亡。在给予亚砷酸钠之前给予槲皮素可阻止HSP70的表达、氧化活性的增加及凋亡的抑制。
脓毒症导致活化的PMNLs中HSPs表达增强。在HSP70表达增强的PMNLs中，氧化活性增加且凋亡受到抑制。HSPs表达增强可能在脓毒症患者PMNL功能调节中起作用。
