Fossati G, Mazzucchelli I, Gritti D, Ricevuti G, Edwards S W, Moulding D A, Rossi M L
Department of Internal Medicine and Therapeutics, IRCCS S. Matteo H., Pavia, Italy.
Int J Mol Med. 1998 Jun;1(6):943-51. doi: 10.3892/ijmm.1.6.943.
GM-CSF can play a crucial role in regulating the neutrophil-mediated inflammatory response. This growth factor is a proliferative stimulus for bone marrow neutrophil stem cell precursors and has at least 3 important roles in regulating neutrophil-mediated immunity: a) a direct effect on the proliferation and development of neutrophil progenitors; b) synergistic activity with other haemopoietic growth factors; c) stimulation of the functional activity of mature neutrophils. The production of GM-CSF may be triggered directly by exogenous factors such as antigens and endotoxins, or indirectly through the release of cytokines by a variety of cells including lymphocytes, activated macrophages and endothelial cells exposed to products of mononuclear phagocytes. Such production of GM-CSF may serve to quickly release mature neutrophils from the bone marrow in response to infections. Moreover, enhancement of the function of mature neutrophils may also augment their ability to migrate to infective sites and then phagocytose and kill pathogens. Increased expression of CD11b/CD18 may play a fundamental part in this mechanism because this receptor is essential for the adhesion of neutrophils to the endothelium. Both phagocytosis and oxidative burst activity increase as a result of the action of GM-CSF and the increased expression of complement- and Fc-receptors can augment opsono-phagocytosis. A further level of neutrophil up-regulation occurs by increasing the functional life span of neutrophils by GM-CSF. Thus, by delaying neutrophil apoptosis, GM-CSF greatly extends the time over which neutrophils may function at inflammatory sites. GM-CSF can thus exert a variety of important regulatory controls of neutrophil function during bacterial infections. Both the number and the functional status of neutrophils is highly regulated by GM-CSF. It is also possible that GM-CSF produced within localised sites of acute inflammation or infection may attract, trap and then activate neutrophils within this site.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）在调节中性粒细胞介导的炎症反应中可发挥关键作用。这种生长因子是骨髓中性粒细胞干细胞前体的增殖刺激物，在调节中性粒细胞介导的免疫方面至少有3个重要作用：a）对中性粒细胞祖细胞的增殖和发育有直接影响；b）与其他造血生长因子具有协同活性；c）刺激成熟中性粒细胞的功能活性。GM-CSF的产生可由外源性因素如抗原和内毒素直接触发，或通过包括淋巴细胞、活化巨噬细胞和暴露于单核吞噬细胞产物的内皮细胞在内的多种细胞释放细胞因子间接触发。GM-CSF的这种产生可能有助于在感染时迅速从骨髓中释放成熟中性粒细胞。此外，增强成熟中性粒细胞的功能也可能增强其迁移到感染部位然后吞噬和杀死病原体的能力。CD11b/CD18表达增加可能在这一机制中起重要作用，因为该受体对中性粒细胞与内皮细胞的黏附至关重要。由于GM-CSF的作用，吞噬作用和氧化爆发活性均增加，补体和Fc受体表达增加可增强调理吞噬作用。GM-CSF通过延长中性粒细胞的功能寿命进一步上调中性粒细胞水平。因此，通过延迟中性粒细胞凋亡，GM-CSF大大延长了中性粒细胞在炎症部位发挥作用的时间。因此，GM-CSF在细菌感染期间可对中性粒细胞功能发挥多种重要的调节控制作用。中性粒细胞的数量和功能状态均受到GM-CSF的高度调节。急性炎症或感染局部部位产生的GM-CSF也有可能吸引、捕获并激活该部位的中性粒细胞。
