Nessa K, Jarstrand C, Johansson A, Camner P
Division of Inhalation Toxicology, Karolinska Institute, Stockholm, Sweden.
Environ Res. 1997;74(1):54-60. doi: 10.1006/enrs.1997.3730.
In vitro interaction of alveolar macrophages (AM) from rats with conidia from Aspergillus fumigatus and Aspergillus candidus as well as inert control particles (amorphous silica) of similar diameter (about 3 microns), was studied. Experimental observations showed that both kinds of conidia were phagocytized significantly faster by AM than were the control particles due to a faster rate of attachment, but even more so due to a faster rate of ingestion. Quantitative nitroblue tetrazolium reduction by AM reflecting their oxidative metabolism and oxygen radical release was increased in response to both kinds of conidia by a factor of 2-3 during the process of phagocytosis, as well as 24 hr after the onset of phagocytosis, compared to corresponding conditions with inert particles and to resting macrophages. The mean pH in phagolysosomes with each of the conidia tended to be higher after 3 hr but was significantly lower after 24 hr than in the phagolysosomes with the control particles. After 3 hr there was a considerable percentage (around 8%) of phagolysosomes with pH > or = 6.5 and after 24 hr there was still a small percentage (0.7%) of such phagolysosomes for each of the conidia. Such a fraction was not observed for the control particles. Electron microscopic studies showed passages between phagolysosomes and AM surface with both kinds of conidia. The occurrence of such unsealed phagolysosomes might explain the percentage of phagolysosomes with high pH. Hence, Aspergillus conidia in unsealed macrophage vacuoles mediate an increased oxygen radical release from the macrophages, a process which in the long run might cause lung damage.
研究了来自大鼠的肺泡巨噬细胞(AM)与烟曲霉和假丝曲霉的分生孢子以及直径相似(约3微米)的惰性对照颗粒(无定形二氧化硅)之间的体外相互作用。实验观察表明,由于附着速率更快,两种分生孢子被AM吞噬的速度明显快于对照颗粒,但更主要是由于摄取速率更快。反映AM氧化代谢和氧自由基释放的定量硝基蓝四氮唑还原在吞噬过程中以及吞噬开始后24小时,对两种分生孢子的反应均比与惰性颗粒和静息巨噬细胞的相应条件增加了2-3倍。与对照颗粒的吞噬溶酶体相比,含有每种分生孢子的吞噬溶酶体在3小时后的平均pH值趋于更高,但在24小时后则明显更低。3小时后,有相当比例(约8%)的吞噬溶酶体pH值≥6.5,24小时后,每种分生孢子仍有一小部分(0.7%)这样的吞噬溶酶体。对照颗粒未观察到这样的比例。电子显微镜研究显示两种分生孢子的吞噬溶酶体与AM表面之间有通道。这种未封闭的吞噬溶酶体的出现可能解释了高pH值吞噬溶酶体的比例。因此,未封闭的巨噬细胞液泡中的曲霉分生孢子介导巨噬细胞释放更多的氧自由基,从长远来看,这一过程可能会导致肺损伤。