Laplante C, Lemaire I
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Am J Pathol. 1990 Jan;136(1):199-206.
To better understand the mechanisms by which alveolar macrophages (AM) are attracted to local sites in the lung, the locomotion of AM in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated. Total bronchoalveolar cells (99% AM) obtained by a nondiscriminating bronchoalveolar lavage procedure migrated toward FMLP over a range of concentrations of 10(-12) M to 10(-6) M. Dose-response experiments showed a biphasic response with two peaks of migration obtained respectively at 5 x 10(-10) M and 10(-8) M. Analysis in the presence and absence of a positive gradient of FMLP revealed that the first peak of migration (5 x 10(-10) M FMLP) corresponded predominantly to chemotactic activity whereas the second peak of migration (10(-8) M FMLP) was associated with chemokinetic activity. To further evaluate these activities of oriented (chemotaxis) vs. random (chemokinesis) migration, AM were separated into two fractions by a two-step bronchoalveolar lavage procedure. Whereas fraction 1 displayed exclusively chemokinesis in response to higher concentrations of FMLP (10(-8) M), fraction 2 was totally unresponsive to FMLP over a wide range of concentrations (5 x 10(-11) M - 10(-7) M). When both fractions were combined, however, the chemotactic response to low concentrations of FMLP (5 x 10(-10) M) was restored. Additional analysis of these two AM fractions indicated that fraction 1 AM had a significantly lower degree of adherence and aggregation than fraction 2 AM. These data suggest that cell-cell cooperation is important for AM chemotactic response to FMLP and that such interaction may involve changes in adherence and aggregation.
为了更好地理解肺泡巨噬细胞（AM）被吸引至肺内局部位点的机制，研究了AM对N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）的运动反应。通过非选择性支气管肺泡灌洗程序获得的总支气管肺泡细胞（99%为AM）在10⁻¹² M至10⁻⁶ M的一系列浓度范围内向FMLP迁移。剂量反应实验显示出双相反应，分别在5×10⁻¹⁰ M和10⁻⁸ M处获得两个迁移峰值。在有和没有FMLP正梯度的情况下进行分析表明，第一个迁移峰值（5×10⁻¹⁰ M FMLP）主要对应趋化活性，而第二个迁移峰值（10⁻⁸ M FMLP）与化学促动活性相关。为了进一步评估定向（趋化作用）与随机（化学促动作用）迁移的这些活性，通过两步支气管肺泡灌洗程序将AM分为两个部分。虽然部分1对较高浓度的FMLP（10⁻⁸ M）仅表现出化学促动作用，但部分2在很宽的浓度范围（5×10⁻¹¹ M - 10⁻⁷ M）内对FMLP完全无反应。然而，当将两个部分合并时，对低浓度FMLP（5×10⁻¹⁰ M）的趋化反应得以恢复。对这两个AM部分的进一步分析表明，部分1的AM比部分2的AM具有显著更低的黏附程度和聚集程度。这些数据表明细胞间合作对于AM对FMLP的趋化反应很重要，并且这种相互作用可能涉及黏附和聚集的变化。
