Lehnert B E, Ortiz J B, London J E, Valdez Y E, Cline A F, Sebring R J, Tietjen G L
Life Sciences Division, Los Alamos National Laboratory, New Mexico 87545.
Exp Lung Res. 1990 Sep-Oct;16(5):451-79. doi: 10.3109/01902149009068820.
We investigated the unstimulated and stimulated migratory activities of lavaged alveolar macrophages (AMs) in vitro over the course of alveolar clearance of three different mass lung burdens of microspheres. Our intent was to uncover potentially important relationships between the migratory behaviors of the AM and the retention kinetics of particles. Groups of adult, male Fischer-344 rats were intratracheally instilled with approximately 86 micrograms (low burden, LB), approximately 1 mg (medium burden, MB), or approximately 3.7 mg (high burden, HB) of polystyrene microspheres (2.13 microns diameter), or with carrier vehicle (phosphate buffered saline, PBS) alone. The lung retention kinetics of the particles were determined over an approximately 170 day period. On days 14, approximately 57, and approximately 85, lavaged AMs were assessed for their abilities to migrate through 5-microns pore membranes in response to inactivated rat serum (unstimulated condition) and yeast-activated rat serum (stimulated condition). The retention characteristics of the three burdens could be satisfactorily described by two-component, negative exponential equations. The kinetics of retention of the LB and MB were similar, although some evidence indicated the MB slightly retarded the lung clearance process. Deposition of the HB resulted in more marked prolongations of both the early, more rapid, and the slower, longer term components of alveolar clearance. The unstimulated migration indices of AMs from the particle-instilled lungs were generally not significantly different from those of AMs from PBS-instilled lungs except for a significant increase in the migration indices of LB AMs at the last assay time. The stimulated migration indices of MB and HB AMs were significantly decreased on assay days 14 and approximately 57. On day approximately 85, however, the migration indices of LB, MB, and HB AMs were all increased above the PBS AMs. Comparisons of the frequency distributions of particles in the unstimulated and stimulated AM that migrated to those in corresponding parent AM populations consistently indicated a preferential migration of particle-free AMs and of AMs with lesser loads of microspheres. The overall results of this study suggest that the unstimulated and stimulated migratory activities of particle-laden AMs are depressed in vitro. Our results also suggest that the migratory activities of generally particle-free AMs may be enhanced over a prolonged period of time following the deposition of particles in the lung.
我们研究了在清除三种不同质量肺负荷微球的肺泡清除过程中，体外灌洗肺泡巨噬细胞（AMs）的未刺激和刺激迁移活性。我们的目的是揭示AMs迁移行为与颗粒滞留动力学之间潜在的重要关系。将成年雄性Fischer-344大鼠分为几组，经气管内分别注入约86微克（低负荷，LB）、约1毫克（中等负荷，MB）或约3.7毫克（高负荷，HB）的聚苯乙烯微球（直径2.13微米），或仅注入载体（磷酸盐缓冲盐水，PBS）。在大约170天的时间内测定颗粒在肺中的滞留动力学。在第14天、大约第57天和大约第85天，评估灌洗的AMs在未激活大鼠血清（未刺激条件）和酵母激活大鼠血清（刺激条件）作用下穿过5微米孔径膜的迁移能力。三种负荷的滞留特征可用双组分负指数方程满意地描述。LB和MB的滞留动力学相似，尽管有一些证据表明MB略微延迟了肺清除过程。HB的沉积导致肺泡清除的早期更快和较慢、更长期的成分均有更明显的延长。除了在最后一次测定时LB AMs的迁移指数显著增加外，来自注入颗粒肺的AMs的未刺激迁移指数通常与来自注入PBS肺的AMs的迁移指数无显著差异。在第14天和大约第57天，MB和HB AMs的刺激迁移指数显著降低。然而，在大约第85天，LB、MB和HB AMs的迁移指数均高于PBS AMs。将未刺激和刺激条件下迁移的AMs中颗粒的频率分布与相应母体AMs群体中的颗粒频率分布进行比较，一致表明无颗粒AMs和微球负荷较小的AMs优先迁移。本研究的总体结果表明，体外载有颗粒的AMs的未刺激和刺激迁移活性受到抑制。我们的结果还表明，在颗粒沉积于肺中后的较长时间内，通常无颗粒的AMs的迁移活性可能会增强。
