Andreoli S P, Mallett C, Williams K, McAteer J A, Rothlein R, Doerschuk C M
Department of Pediatrics, Indiana University School of Medicine, Indianapolis.
Kidney Int. 1994 Oct;46(4):1100-9. doi: 10.1038/ki.1994.372.
To determine the susceptibility of human peritoneal mesothelial cells to injury mediated by activated polymorphonuclear leukocytes (PMNs), we exposed cultured human peritoneal mesothelial cells to 1250, 2500, 3750, and 5000 PMNs/mm3 activated with 50 ng/ml phorbol myristate acetate (PMA) or with 10(-7) FMLP/cytochalasin B for one to five hours. PMN adhesion to mesothelial cells was determined with radiolabeled PMNs. Mesothelial cell injury was determined in five different cell lines by measuring ATP depletion and 51chromium release. In each mesothelial cell line, PMN adhesion was significantly (P < 0.001) increased when PMNs were activated; 64 +/- 1.0 to 92.5 +/- 7.0% of the activated PMNs were adherent to mesothelial cells compared to 6 +/- 1.8 to 27 +/- 2.4% of resting PMNs. Mesothelial cells responded to PMN mediated injury with a fall in ATP levels and 51chromium release that was significant (P < 0.05) by three to four hours. At five hours, ATP levels were markedly depressed to 5 to 41% of control values. Increasing concentrations of activated PMNs caused significantly (P < 0.05) greater mesothelial cell injury as determined by ATP depletion and 51chromium release. PMN adhesion, ATP depletion and 51chromium release were significantly (P < 0.01) prevented by an anti-CD18 monoclonal antibody that inhibits the CD11/CD18 adhesion molecule complex on PMNs. Similar injury and protection from injury was demonstrated when mesothelial cells were exposed to PMNs activated with FMLP/cytochalasin B.(ABSTRACT TRUNCATED AT 250 WORDS)
为了确定人腹膜间皮细胞对活化多形核白细胞（PMN）介导损伤的易感性，我们将培养的人腹膜间皮细胞暴露于用50 ng/ml佛波酯肉豆蔻酸乙酸酯（PMA）或10⁻⁷甲酰甲硫氨酸-亮氨酸-苯丙氨酸（FMLP）/细胞松弛素B激活的1250、2500、3750和5000个PMN/mm³中1至5小时。用放射性标记的PMN测定PMN与间皮细胞的黏附。通过测量ATP消耗和⁵¹铬释放来确定五种不同细胞系中的间皮细胞损伤。在每个间皮细胞系中，当PMN被激活时，PMN黏附显著（P < 0.001）增加；与静息PMN的6% ± 1.8%至27% ± 2.4%相比，64% ± 1.0%至92.5% ± 7.0%的活化PMN黏附于间皮细胞。间皮细胞对PMN介导的损伤反应是ATP水平下降和⁵¹铬释放，在3至4小时时显著（P < 0.05）。在5小时时，ATP水平显著降低至对照值的5%至41%。如通过ATP消耗和⁵¹铬释放所确定的，活化PMN浓度增加导致间皮细胞损伤显著（P < 0.05）加重。抗CD18单克隆抗体可显著（P < 0.01）阻止PMN黏附、ATP消耗和⁵¹铬释放，该抗体抑制PMN上的CD11/CD18黏附分子复合物。当间皮细胞暴露于用FMLP/细胞松弛素B激活的PMN时，也显示出类似的损伤和对损伤的保护。（摘要截断于250字）
