Gamelli R L, He L K, Liu H, Ricken J D
Loyola University Medical Center, Shock Trauma Institute and Department of Surgery, Maywood, Illinois 60153, USA.
J Trauma. 1998 Mar;44(3):469-74. doi: 10.1097/00005373-199803000-00008.
Suppressed granulocyte and macrophage growth after burn infection or endotoxicosis appears to be mediated by macrophage-derived products. In this study, we found that after burn, burn plus infection, or endotoxicosis, peritoneal-elicited macrophages or bone marrow cells released increased amounts of prostaglandin E2 (PGE2) and inhibited growth of granulocyte-macrophage progenitor cells (GM-CFC). PGE2, when added in culture, inhibited in vitro GM-CFC growth in a dose-dependent manner. Pretreatment of bone marrow cells with either dibutyryl cyclic adenosine monophosphate or Forskolin in vitro mimicked the PGE2 inhibition, further aggravated the inhibition induced by burn, burn plus infection, or endotoxicosis, and was not blocked by co-culture with indomethacin. Pretreatment of bone marrow cells with SQ22536, an adenylate cyclase inhibitor, significantly restored the suppressed GM-CFC growth found after burn, burn plus infection, or endotoxicosis. Alterations in myeloid production after burn infection appear to be related in part to the level of intracellular cyclic adenosine monophosphate for the GM-CFC and are responsive to PGE2.
烧伤感染或内毒素血症后粒细胞和巨噬细胞生长受抑制，似乎是由巨噬细胞衍生产物介导的。在本研究中，我们发现烧伤、烧伤加感染或内毒素血症后，腹腔引出的巨噬细胞或骨髓细胞释放出增加量的前列腺素E2（PGE2），并抑制粒细胞-巨噬细胞祖细胞（GM-CFC）的生长。PGE2在培养中添加时，以剂量依赖方式抑制体外GM-CFC生长。用二丁酰环磷酸腺苷或福司可林在体外预处理骨髓细胞模拟了PGE2抑制作用，进一步加重了烧伤、烧伤加感染或内毒素血症诱导的抑制作用，且与吲哚美辛共培养不能阻断该作用。用腺苷酸环化酶抑制剂SQ22536预处理骨髓细胞，显著恢复了烧伤、烧伤加感染或内毒素血症后发现的受抑制的GM-CFC生长。烧伤感染后髓系生成的改变似乎部分与GM-CFC的细胞内环磷酸腺苷水平有关，且对PGE2有反应。
