Lane T A, Lamkin G E
Blood. 1986 Aug;68(2):351-4.
We previously showed that an artificial blood substitute containing perfluorocarbons, Fluosol-DA, inhibited both neutrophil migration and adherence, due to its detergent component, Pluronic F-68. The purpose of the studies we report here was to determine if Fluosol or Pluronic might also reduce in vivo neutrophil migration and impair host resistance to bacterial infection. We studied in vivo PMN migration by injecting mice intraperitoneally (IP) with glycogen, followed by intravenous (IV) infusion of saline, Fluosol, or Pluronic. Peritoneal lavage after eight hours showed a significant decrease in the accumulation of PMN in lavage fluids of animals given either Fluosol or Pluronic (control--.19 +/- .03 X 10(6) PMN/mL, glycogen--1.35 +/- .14; glycogen/Fluosol--0.63 +/- .12; glycogen/Pluronic--0.69 +/- .07). We ascertained the effect of Fluosol and Pluronic on infection mortality by injecting mice IV with saline, Fluosol, or Pluronic, followed by a quantity of E coli (0.6 X 10(7] IP shown in preliminary studies to kill 20% to 50% of the mice in 24 hours. The 24-hour mortality was 14/45-saline, 24/32-Fluosol (chi 2 = 17.1; P less than .001) and 17/23 - Pluronic (chi = 11.2; P less than .001). Neither Fluosol nor Pluronic caused mortality without E coli. The increase in infection mortality occurred when Fluosol was given either two hours before, or simultaneously with E coli, but only with the simultaneous administration of bacteria and Pluronic. Pluronic did not alter reticuloendothelial system (RES) clearance function. These studies indicate that, in an animal model, Fluosol-DA, due to its detergent component Pluronic F-68, impaired neutrophil delivery to an inflammatory locus, and resulted in an increased rate of infection mortality. Since Pluronic did not result in RES blockade, but did impair the delivery of PMN to an inflammatory locus, our results suggest that the latter effect is responsible for the increase in infection mortality.
我们之前曾表明，一种含全氟碳化合物的人工血液代用品氟索（Fluosol-DA），因其去污剂成分普流罗尼克F-68（Pluronic F-68）而抑制中性粒细胞的迁移和黏附。我们在此报告的研究目的是确定氟索或普流罗尼克是否也会降低体内中性粒细胞的迁移，并损害宿主对细菌感染的抵抗力。我们通过给小鼠腹腔内注射糖原，随后静脉输注生理盐水、氟索或普流罗尼克，来研究体内的中性粒细胞迁移情况。八小时后进行腹腔灌洗，结果显示，给予氟索或普流罗尼克的动物灌洗液中中性粒细胞的积聚显著减少（对照组——0.19±0.03×10⁶个中性粒细胞/毫升，糖原组——1.35±0.14；糖原/氟索组——0.63±0.12；糖原/普流罗尼克组——0.69±0.07）。我们通过给小鼠静脉注射生理盐水、氟索或普流罗尼克，随后注射一定量的大肠杆菌（初步研究表明，腹腔注射0.6×10⁷个大肠杆菌可在24小时内杀死20%至50%的小鼠），来确定氟索和普流罗尼克对感染死亡率的影响。24小时死亡率分别为：生理盐水组14/45，氟索组24/32（χ² = 17.1；P＜0.001），普流罗尼克组17/23（χ² = 11.2；P＜0.001）。在没有大肠杆菌的情况下，氟索和普流罗尼克都不会导致死亡。当在大肠杆菌注射前两小时或同时给予氟索时，感染死亡率会增加，但只有在同时给予细菌和普流罗尼克时才会如此。普流罗尼克不会改变网状内皮系统（RES）的清除功能。这些研究表明，在动物模型中，氟索-DA因其去污剂成分普流罗尼克F-68，损害了中性粒细胞向炎症部位的输送，并导致感染死亡率上升。由于普流罗尼克不会导致RES阻滞，但确实损害了中性粒细胞向炎症部位的输送，我们的结果表明，后一种效应是感染死亡率上升的原因。
