Høgevold H E, Lyberg T, Kähler H, Reikerås O
Research Forum, Ullevål University Hospital, Oslo, Norway.
Eur Surg Res. 1996;28(3):190-200. doi: 10.1159/000129457.
The aim of this study was to characterize the changes in the quantitative expression of beta 2-integrins and L-selectin detected by means of fluorochrome-conjugated monoclonal antibodies and flow cytometry on leukocytes in the systemic circulation after a major musculoskeletal trauma, i.e. hip replacement surgery, and to relate these changes to parameters of the acute-phase response [plasma acute-phase reactants (C-reactive protein, CRP, and interleukin-6, IL-6) and parameters of coagulation activation (thrombin-antithrombin III complexes, TAT)]. Eight patients with either primary or secondary osteoarthritis of the hip received uncemented total hip prostheses. LFA-1 (CD11a/CD18) was upregulated on granulocytes during the operation. MAC-1 (CD11b/CD18) expression on monocytes increased to peak levels 20 h after surgery, whereas the L-selectin (CD62L) expression on monocytes and granulocytes reached peak values at the end of surgery. The changes in expression of LFA-1 on monocytes, MAC-1 on granulocytes and p150,95 (CD11c/CD18) on monocytes and granulocytes during and after the operation did not reach statistical significance. TAT and IL-6 increased during surgery and reached peak values at the end of the operation and 20 h after surgery, respectively. In contrast, CPR concentrations increased after surgery with peak levels 44 h postoperatively. Significant upregulation of LFA-1 on granulocytes and L-selectin on monocytes and granulocytes preceded the increase in IL-6 which again preceded the increase in CRP. However, the up- or downregulation of leukocyte beta 2-integrins and L-selectin during and after surgery was not significantly correlated with the increase in IL-6. The increases in TAT correlated well with the upregulation of L-selectin on monocytes, but not with the beta 2-integrins known to participate in the coagulation process in vitro. The rise in CRP was inversely correlated with the maximal increase in expression of MAC-1 on monocytes. In conclusion, the changes in leukocyte adhesion molecules during and after surgery indicate changes in critical leukocyte functions. The lack of correlation between quantitative up- and downregulation of leukocyte beta 2-integrins and parameters of the acute phase response suggests that these processes are regulated through independent pathways or that functional up- and downregulation of adhesion molecules, shedding, leukocyte-endothelial adhesion and mobilization of new unactivated cells may result in a net estimate of leukocyte activation not suspected to be positively correlated to acute-phase reactants.
本研究的目的是,通过使用荧光染料偶联的单克隆抗体和流式细胞术,对大的肌肉骨骼创伤(即髋关节置换手术)后体循环中白细胞上β2整合素和L选择素的定量表达变化进行表征,并将这些变化与急性期反应参数[血浆急性期反应物(C反应蛋白,CRP,和白细胞介素-6,IL-6)以及凝血激活参数(凝血酶-抗凝血酶III复合物,TAT)]相关联。八名患有原发性或继发性髋骨关节炎的患者接受了非骨水泥型全髋关节假体置换。手术过程中粒细胞上的淋巴细胞功能相关抗原-1(LFA-1,CD11a/CD18)上调。单核细胞上的巨噬细胞抗原-1(MAC-1,CD11b/CD18)表达在术后20小时增加至峰值水平,而单核细胞和粒细胞上的L选择素(CD62L)表达在手术结束时达到峰值。手术期间及术后单核细胞上LFA-1、粒细胞上MAC-1以及单核细胞和粒细胞上p150,95(CD11c/CD18)表达的变化未达到统计学意义。TAT和IL-6在手术期间增加,并分别在手术结束时和术后20小时达到峰值。相比之下,CRP浓度在术后增加,术后44小时达到峰值水平。粒细胞上LFA-1以及单核细胞和粒细胞上L选择素的显著上调先于IL-6的增加,而IL-6的增加又先于CRP的增加。然而,手术期间及术后白细胞β2整合素和L选择素的上调或下调与IL-6的增加无显著相关性。TAT的增加与单核细胞上L选择素的上调密切相关,但与已知在体外参与凝血过程的β2整合素无关。CRP的升高与单核细胞上MAC-1表达的最大增加呈负相关。总之,手术期间及术后白细胞黏附分子的变化表明关键白细胞功能发生了改变。白细胞β2整合素的定量上调和下调与急性期反应参数之间缺乏相关性,这表明这些过程是通过独立途径调节的,或者黏附分子的功能性上调和下调、脱落、白细胞-内皮细胞黏附以及新的未活化细胞的动员可能导致白细胞活化的净估计值与急性期反应物无正相关。