Van Hal P T, Hopstaken-Broos J P, Wijkhuijs J M, Te Velde A A, Figdor C G, Hoogsteden H C
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
J Immunol. 1992 Aug 15;149(4):1395-401.
IL-4 has multiple biologic activities and it has been shown to have effects on B and T lymphocytes, mast cells, NK cells, and monocytes. We studied the influence of IL-4 on the expression of cell membrane determinants, in particular aminopeptidase-N (CD13) and Fc epsilon RIIb (CD23), on human peripheral blood monocytes. We compared the response of monocytes with the response of human alveolar macrophages and monocytic cell lines (U937 and THP1), as mature and more immature representatives of the mononuclear phagocyte system, respectively. A dose-dependent increase of the expression of CD13 Ag was observed when monocytes were cultured with IL-4. Kinetic analyses revealed that this induction was maximal after 2 to 3 days of culture and resembled the kinetics of IL-4-induced expression of Fc epsilon RIIb on monocytes. This IL-4-induced increase was absent when monocytes were cultured with IL-4 and an anti-IL-4 antiserum. Concomitantly, an IL-4-induced increase in leucine-aminopeptidase activity could be observed. Northern blot analysis showed that incubation of monocytes with IL-4 induced a marked increase in CD13 mRNA. Alveolar macrophages also exhibited an increase in CD13 Ag expression when exposed to IL-4. Surprisingly, IL-4 was unable to induce expression of Fc epsilon RIIb on alveolar macrophages. U937 and THP1 cells did not show an induction of CD13 Ag when cultured in the presence of IL-4. However, IL-4 did induce the expression of Fc epsilon RIIb on both cell lines, suggesting the presence of functional IL-4R. Our data demonstrate that IL-4 increases the expression of CD13 Ag on monocytes. This IL-4-induced increase can also be observed in more mature monocytic cells such as alveolar macrophages, but is absent in immature cells such as U937 or THP1 cells. This is functionally accompanied by an increase in leucine-aminopeptidase activity and may be part of the general activation of monocytes/macrophages by IL-4. In conclusion, the data suggest that IL-4 responsiveness, in particular the induction of CD13 Ag and Fc epsilon RIIb expression, may be dependent on the stage of maturation of monocytes/macrophages.
白细胞介素-4具有多种生物学活性，已证明它对B淋巴细胞、T淋巴细胞、肥大细胞、自然杀伤细胞和单核细胞有作用。我们研究了白细胞介素-4对人外周血单核细胞膜决定簇表达的影响，特别是氨肽酶-N（CD13）和FcεRIIb（CD23）。我们将单核细胞的反应与人类肺泡巨噬细胞和单核细胞系（U937和THP1）的反应进行了比较，它们分别是单核吞噬细胞系统成熟和更不成熟的代表。当单核细胞与白细胞介素-4一起培养时，观察到CD13抗原表达呈剂量依赖性增加。动力学分析表明，这种诱导在培养2至3天后达到最大值，类似于白细胞介素-4诱导单核细胞上FcεRIIb表达的动力学。当单核细胞与白细胞介素-4和抗白细胞介素-4抗血清一起培养时，这种由白细胞介素-4诱导的增加不存在。同时，可以观察到白细胞介素-4诱导亮氨酸氨肽酶活性增加。Northern印迹分析表明，单核细胞与白细胞介素-4孵育可诱导CD13 mRNA显著增加。肺泡巨噬细胞在暴露于白细胞介素-4时也表现出CD13抗原表达增加。令人惊讶的是，白细胞介素-4无法诱导肺泡巨噬细胞上FcεRIIb的表达。当U937和THP1细胞在白细胞介素-4存在下培养时，未显示出CD13抗原的诱导。然而，白细胞介素-4确实诱导了这两种细胞系上FcεRIIb的表达，表明存在功能性白细胞介素-4受体。我们的数据表明，白细胞介素-4增加了单核细胞上CD13抗原的表达。这种由白细胞介素-4诱导的增加在更成熟的单核细胞如肺泡巨噬细胞中也可以观察到，但在不成熟细胞如U937或THP1细胞中不存在。这在功能上伴随着亮氨酸氨肽酶活性的增加，可能是白细胞介素-4对单核细胞/巨噬细胞进行一般激活的一部分。总之，数据表明白细胞介素-4的反应性，特别是CD13抗原和FcεRIIb表达的诱导，可能取决于单核细胞/巨噬细胞的成熟阶段。
