Maye I, de Fraissinette A, Cruz-Orive L M, Andersen E, Niederlander C, Bueb W, Froehlich C, Schreier M, Vonderscher J, Richter F, Cordier A, Gehr P
Institute of Anatomy, University of Bern, Switzerland.
Cell Biol Toxicol. 1998 Dec;14(6):411-8. doi: 10.1023/a:1007547612154.
The aim of this study was to compare two types of cyclosporin (Cs) particles, SDZ OXL 400 and SDZ IMM 125, the latter being more hydrophilic, to understand their uptake by airway macrophages. Alveolar macrophages (AM), harvested by bronchoalveolar lavage (BAL) of hamster lungs, were cultured with two different doses (0.1 mg and 0.5 mg) for 1 h, 6 h, and 24 h. Control incubations without Cs particles or with latex particles were carried out simultaneously. Cell viability, cell activation (i.e., respiratory burst, interleukin-6 (IL-6) synthesis) and mean volume of particles phagocytosed per macrophage were measured. Both types of Cs particles did not modify the AM viability, and failed to induce IL-6 synthesis during phagocytosis but slightly decreased the cell oxidative respiratory burst. The comparison between SDZ OXL 400 and SDZ IMM 125 showed that for the lower dose the mean volume of both Cs types phagocytosed was similar at 1 h and 6 h. At 24 h an increase of the mean volume phagocytosed was seen for SDZ IMM 125 but not for SDZ OXL 400. For the higher dose the mean volume of SDZ IMM 125 phagocytosed was higher than SDZ OXL 400 at 1 h and 6 h and comparable for both types at 24 h. SDZ IMM 125 particles were phagocytosed more rapidly than SDZ OXL 400. The mean volume of phagocytosed latex particles increased with time and dose and was higher than for both Cs particle types. In conclusion, AM were seen to phagocytose particles of different physical properties (i.e., form, size, and shape), chemical properties (i.e., inert or peptidic) and degrees of hydrophilicity in a different manner.
本研究的目的是比较两种环孢素（Cs）颗粒，即SDZ OXL 400和SDZ IMM 125（后者亲水性更强），以了解气道巨噬细胞对它们的摄取情况。通过对仓鼠肺部进行支气管肺泡灌洗（BAL）收获肺泡巨噬细胞（AM），将其与两种不同剂量（0.1 mg和0.5 mg）的颗粒培养1小时、6小时和24小时。同时进行不含Cs颗粒或含乳胶颗粒的对照培养。测量细胞活力、细胞活化（即呼吸爆发、白细胞介素-6（IL-6）合成）以及每个巨噬细胞吞噬颗粒的平均体积。两种类型的Cs颗粒均未改变AM的活力，在吞噬过程中未能诱导IL-6合成，但略微降低了细胞氧化呼吸爆发。SDZ OXL 400和SDZ IMM 125之间的比较表明，对于较低剂量，两种Cs类型在1小时和6小时吞噬的平均体积相似。在24小时时，SDZ IMM 125吞噬的平均体积增加，而SDZ OXL 400则没有。对于较高剂量，SDZ IMM 125在1小时和6小时吞噬的平均体积高于SDZ OXL 400，在24小时时两种类型相当。SDZ IMM 125颗粒比SDZ OXL 400吞噬得更快。吞噬乳胶颗粒的平均体积随时间和剂量增加，且高于两种Cs颗粒类型。总之，发现AM以不同方式吞噬具有不同物理性质（即形态、大小和形状）、化学性质（即惰性或肽性）和亲水性程度的颗粒。
