Zhou A Q, Herriott M J, Leu R W
Biomedical Division, Samuel Roberts Noble Foundation, Inc., Ardmore, Oklahoma 73402.
J Leukoc Biol. 1991 Nov;50(5):453-63. doi: 10.1002/jlb.50.5.453.
We investigated the effects of bacterial lipopolysaccharide (LPS), immune complexes (IC), and C3b opsonized zymosan (AZ) alone and in combination with interferon-gamma (IFN-gamma) priming on macrophage synthesis and secretion of C1q. Our results indicated that LPS, IC, and AZ alone stimulated C1q mRNA and secretion in the absence of IFN-gamma. The increase in mRNA accumulation was detectable after 3 h, peaked at 6 h and was maintained at constitutive levels for 24 h. There was a corresponding early burst of increased secretion of functional C1q after 3 to 6 h which declined rapidly after 9 to 24 h culture of LPS-stimulated macrophages. Priming of macrophages with IFN-gamma and simultaneous triggering with LPS, IC, or AZ produced additive rather than synergistic increases in C1q mRNA accumulation. These same agents inhibited constitutive secretion of C1q in the absence of IFN-gamma priming as determined by autoradiographic analysis of metabolically radiolabeled secretory C1q. Triggering of IFN-gamma primed macrophages with LPS, IC, or AZ also markedly suppressed the increased rate of C1q secretion induced by IFN-gamma in a dose-related fashion. A corresponding dose-dependent increased accumulation of endogenous C1q in cell lysates was detected by Western blot analysis of macrophages which had been stimulated by LPS, IC, or AZ alone or in combination with IFN-gamma. Our findings indicate that LPS as well as FcR and C3bR triggering agents stimulate early and sustained C1q synthesis accompanied by an early and short-lived burst of C1q secretion which rapidly diminished and results in an increased intracellular accumulation of C1q due to ongoing synthesis. IFN-gamma appeared to further amplify the same kinetics of increased C1q mRNA accumulation and decreased extracellular accumulation mediated by LPS, IC, and ZM. Our results suggest that LPS, IC, and AZ alone or in combination with IFN-gamma stimulate early C1q production to modulate macrophage effector functions followed by an inhibition of C1q secretion when the activation process has been culminated.
我们研究了细菌脂多糖（LPS）、免疫复合物（IC）和C3b调理酵母聚糖（AZ）单独作用以及与干扰素-γ（IFN-γ）预刺激联合作用对巨噬细胞C1q合成与分泌的影响。我们的结果表明，在无IFN-γ的情况下，LPS、IC和AZ单独均可刺激C1q mRNA表达及分泌。3小时后可检测到mRNA积累增加，6小时达到峰值，并在24小时内维持在基础水平。LPS刺激的巨噬细胞培养9至24小时后，3至6小时出现相应的功能性C1q分泌早期爆发，随后迅速下降。用IFN-γ预刺激巨噬细胞并同时用LPS、IC或AZ触发，可使C1q mRNA积累呈相加而非协同增加。通过对代谢性放射性标记的分泌型C1q进行放射自显影分析确定，在无IFN-γ预刺激的情况下，这些相同的试剂可抑制C1q的组成性分泌。用LPS、IC或AZ触发IFN-γ预刺激的巨噬细胞，也以剂量相关方式显著抑制IFN-γ诱导的C1q分泌增加率。通过对单独或与IFN-γ联合用LPS、IC或AZ刺激的巨噬细胞进行蛋白质印迹分析，检测到细胞裂解物中内源性C1q的积累相应地呈剂量依赖性增加。我们的研究结果表明，LPS以及FcR和C3bR触发剂可刺激早期且持续的C1q合成，伴随C1q分泌的早期且短暂爆发，随后迅速减少，由于持续合成导致细胞内C1q积累增加。IFN-γ似乎进一步放大了由LPS、IC和ZM介导的C1q mRNA积累增加和细胞外积累减少的相同动力学。我们的结果表明，LPS、IC和AZ单独或与IFN-γ联合可刺激早期C1q产生以调节巨噬细胞效应功能，当激活过程达到顶点时随后抑制C1q分泌。
