Miller-Graziano C L, Kodys K, Gonzalez F, Fudem G M
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655, USA.
Shock. 1994 May;1(5):317-24.
In investigating various mechanisms for continued elevated tumor necrosis factor alpha (TNF alpha) production in trauma patients' monocytes (Mphi), we examined TNF receptor (TNFR) levels on the patients' Mphi as a possible altered pathway leading to continued autocrine TNF alpha stimulation. Mphi TNFR synthesis and shedding are both increased as TNF alpha protein production increases. In fatal meningococcal infections, TNFR shedding fails to pace TNF alpha production. Here, isolated normal and trauma patients' Mphi (injury severity score greater than 30), were examined by flow cytometry using phycoerythrin-labeled TNF alpha to detect increased or decreased TNFR expression concomitant to Mphi production of secreted TNF alpha (as measured in the LM bioassay). Immunoaberrant patients (mitogen proliferation depressed) had reduction in detectable TNF alpha binding by their TNFR, while Mphi from immunocompetent (normal mitogen response) trauma patients' Mphi had a TNFR expression intensity comparable to normals' Mphi. Upon in vitro stimulation of TNF alpha (IFN gamma + muramyl dipeptide) normals' and immunocompetent patients' MO TNFR expression is decreased for the entire 18 h period during which secreted TNF alpha is produced, but immunoaberrant trauma patients' Mphi increased their TNFR expression, while concomitantly producing both secreted and cell-associated TNF alpha protein. Patients' Mphi with highly elevated TNF alpha levels are still expressing high levels of TNFR and capable of auto-stimulating TNF alpha production. This elevated TNFR expression could be due to reduced shedding, overproduction of TNFR, or both.
在研究创伤患者单核细胞（Mphi）中肿瘤坏死因子α（TNFα）持续高水平产生的各种机制时，我们检测了患者Mphi上的TNF受体（TNFR）水平，作为可能导致持续自分泌TNFα刺激的改变途径。随着TNFα蛋白产生增加，Mphi的TNFR合成和脱落均增加。在致命的脑膜炎球菌感染中，TNFR脱落无法跟上TNFα的产生速度。在此，通过流式细胞术使用藻红蛋白标记的TNFα检测分离的正常人和创伤患者的Mphi（损伤严重度评分大于30），以检测与分泌型TNFα的Mphi产生相关的TNFR表达增加或减少（如在LM生物测定中测量）。免疫异常患者（丝裂原增殖受抑制）其TNFR可检测到的TNFα结合减少，而来自免疫功能正常（正常丝裂原反应）创伤患者的Mphi的TNFR表达强度与正常人的Mphi相当。在体外刺激TNFα（IFNγ+胞壁酰二肽）后，在分泌型TNFα产生的整个18小时期间，正常人和免疫功能正常患者的Mphi的TNFR表达均降低，但免疫异常创伤患者的Mphi增加了其TNFR表达，同时产生分泌型和细胞相关的TNFα蛋白。TNFα水平高度升高的患者Mphi仍表达高水平的TNFR，并能够自刺激TNFα产生。这种升高的TNFR表达可能是由于脱落减少、TNFR产生过多或两者兼而有之。
