A NEW ROLE FOR COMPLEMENT IN EXPERIMENTAL MEMBRANOUS NEPHROPATHY IN RATS
A NEW ROLE FOR COMPLEMENT IN EXPERIMENTAL MEMBRANOUS NEPHROPATHY IN RATS
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DOI：
10.1172/jci109987
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发表时间：
1980-01-01
影响因子：
15.9
通讯作者：
COUSER, WG
中科院分区：
文献类型：
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作者：
SALANT, DJ;BELOK, S;COUSER, WG
补体[c]在介导免疫性肾脏疾病中唯一已确定的作用涉及白细胞趋化因子和中性粒细胞依赖的肾小球损伤的阐述。在实验性膜性肾病的被动型Heymann肾炎(PHN)模型中，大鼠注射抗大鼠近端小管刷状边界抗原(Fx1a)的绵羊抗体(Fx1a)，形成绵羊Ig G和大鼠成分3(C3)的上皮下沉积，5d后出现大量蛋白尿，肾小球炎性改变不明显。为了研究C在调节PHN蛋白尿中的作用，16只大鼠在注射抗体前每天给予眼镜蛇毒素因子治疗，以将C3水平维持在治疗前的10%，并与16只未治疗的对照组进行比较。C3耗竭大鼠5天的蛋白尿被消除(4。+-。1，控制70。+-。15 mg/d，P<；0.001)，尽管两组125I标记抗体在肾脏中的沉积相同(188.+-)。35对191。+-22微克免疫球蛋白/2肾，P>；0.05)。致肾剂量的非补体固定F(ab‘)2部分和抗Fx1a抗体2亚类都能产生不含C3的Ig上皮下沉积，但尽管肾小球沉积高达70µg/2的Gamma肾，蛋白尿并未出现。肾小球沉积低至60微克的γ-1可在体内产生C3固定和大量蛋白尿。从注射抗体至出现蛋白尿，PHN组织学上未检测到中性粒细胞渗出物。与中性粒细胞计数正常的6只对照组相比，中性粒细胞耗尽至200/mm3的5只PHN大鼠的蛋白尿并未减少。9.6比25。+-10.4 mg/d，P>；0.05)。显然，膜性肾病PHN模型中的蛋白尿是C依赖的，并强烈提示中性粒细胞非依赖性机制。C系统在介导免疫性肾小球损伤中的新作用被确认。
The only established role for complement [c] in mediating immunologic renal disease involves elaboration of leukochemotactic factors and neutrophil-dependent glomerular injury. In the passive Heymann nephritis (PHN) model of experimental membranous nephropathy, rats injected with sheep antibody to rat proximal tubular brush border antigen (Fx1A) form subepithelial deposits of sheep IgG and rat component 3 (C3), and develop heavy proteinuria after 5 days without glomerular inflammatory changes. To study the role of C in mediating proteinuria in PHN, 16 rats were treated daily with cobra venom factor from before antibody injection to maintain C3 levels at < 10% of pretreatment values and compared to 16 untreated controls. Proteinuria at 5 days was abolished in C3-depleted rats (4 .+-. 1, controls 70 .+-. 15 mg/d, P < 0.001), although renal deposition of 125I-labeled antibody was the same in both groups (188 .+-. 35 vs. 191 .+-. 22 .mu.g IgG/2 kidneys, P > 0.05). Nephritogenic doses of both the noncomplement-fixing F(ab'')2 portion and the .gamma.2 subclass of anti-Fx1A IgG produced subepithelial deposits of Ig without C3, but proteinuria did not occur despite glomerular deposition of up to 70 .mu.g/2 kidneys of .gamma.2. Glomerular deposition of as little as 60 .mu.g of .gamma.1 produced C3 fixation in vivo and heavy proteinuria. No neutrophil exudate could be detected histologically in PHN from the time of antibody injection through development of proteinuria. Proteinuria in five PHN rats depleted of neutrophils to < 200/mm3 with anti-neutrophil serum was not reduced compared to 6 controls with normal neutrophil counts (34 .+-. 9.6 vs. 25 .+-. 10.4 mg/d, P > 0.05). Evidently proteinuria in the PHN model of membranous nephropathy is C-dependent and strongly suggest a neutrophil-independent mechanism. A new role for the C system in mediating immunologic glomerular injury is identified.