不溶性和可溶性免疫复合物通过不同的激活机制激活中性粒细胞：细胞因子预刺激诱导的功能反应变化。
Insoluble and soluble immune complexes activate neutrophils by distinct activation mechanisms: changes in functional responses induced by priming with cytokines.
作者信息
Fossati G, Bucknall R C, Edwards S W
机构信息
School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB, UK.
出版信息
Ann Rheum Dis. 2002 Jan;61(1):13-9. doi: 10.1136/ard.61.1.13.
BACKGROUND
Rheumatoid synovial fluid contains both soluble and insoluble immune complexes that can activate infiltrating immune cells such as neutrophils.
OBJECTIVES
To determine if these different complexes activate neutrophils through similar or different receptor signalling pathways. In particular, to determine the circumstances which result in the secretion of tissue damaging reactive oxygen metabolites and granule enzymes.
METHODS
Blood neutrophils were incubated with synthetic soluble and insoluble immune complexes and the ability to generate reactive oxidants tested by luminescence or spectrophotometric assays that distinguished between intracellular and extracellular production. Degranulation of myeloperoxidase and lactoferrin was determined by western blotting. The roles of FcgammaRII (CD32) and FcgammaRIIIb (CD16) were determined by incubation with Fab/F(ab')(2) fragments before activation. The effect of cytokine priming was determined by incubation with GM-CSF.
RESULTS
Insoluble immune complexes activated unprimed neutrophils, but most of the oxidants produced were intracellular. This activation required FcgammaRIIIb, but not FcgammaRII function. Soluble complexes failed to activate unprimed neutrophils but generated a rapid and extensive secretion of reactive oxygen metabolites when the cells were primed with granulocyte-macrophage colony stimulating factor (GM-CSF). This activity required both FcgammaRII and FcgammaRIIIb function. Insoluble immune complexes activated the release of granule enzymes from primed or unprimed neutrophils, but the kinetics of release did not parallel those of secretion of reactive oxygen metabolites. Only primed neutrophils released enzymes in response to soluble complexes.
CONCLUSIONS
Soluble and insoluble immune complexes activate neutrophils by separate receptor signalling pathways. Profound changes in neutrophil responsiveness to these complexes occur after cytokine priming.
背景
类风湿性滑液中含有可溶性和不溶性免疫复合物，它们可激活浸润的免疫细胞，如中性粒细胞。
目的
确定这些不同的复合物是否通过相似或不同的受体信号通路激活中性粒细胞。特别是确定导致组织损伤性活性氧代谢产物和颗粒酶分泌的情况。
方法
将血液中的中性粒细胞与合成的可溶性和不溶性免疫复合物一起孵育，并通过区分细胞内和细胞外产生的发光或分光光度测定法检测产生活性氧化剂的能力。通过蛋白质印迹法测定髓过氧化物酶和乳铁蛋白的脱颗粒情况。在激活前，通过与Fab/F(ab')(2)片段孵育来确定FcγRII（CD32）和FcγRIIIb（CD16）的作用。通过与粒细胞巨噬细胞集落刺激因子（GM-CSF）孵育来确定细胞因子预刺激的效果。
结果
不溶性免疫复合物激活未预刺激的中性粒细胞，但产生的大多数氧化剂是细胞内的。这种激活需要FcγRIIIb，但不需要FcγRII的功能。可溶性复合物未能激活未预刺激的中性粒细胞，但当细胞用粒细胞巨噬细胞集落刺激因子（GM-CSF）预刺激时，会产生活性氧代谢产物的快速大量分泌。这种活性需要FcγRII和FcγRIIIb的功能。不溶性免疫复合物激活了预刺激或未预刺激的中性粒细胞中颗粒酶的释放，但释放动力学与活性氧代谢产物的分泌动力学不平行。只有预刺激的中性粒细胞对可溶性复合物有反应而释放酶。
结论
可溶性和不溶性免疫复合物通过不同的受体信号通路激活中性粒细胞。细胞因子预刺激后，中性粒细胞对这些复合物的反应性发生了深刻变化。
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