IgA诱导人系膜细胞活化：不依赖于FcalphaR1（CD89）。

IgA induced activation of human mesangial cells: independent of FcalphaR1 (CD 89).

作者信息

Diven S C, Caflisch C R, Hammond D K, Weigel P H, Oka J A, Goldblum R M

机构信息

Department of Pediatrics, University of Texas Medical Branch, Galveston 77555-0373, USA.

出版信息

Kidney Int. 1998 Sep;54(3):837-47. doi: 10.1046/j.1523-1755.1998.00054.x.

DOI:10.1046/j.1523-1755.1998.00054.x

PMID:9734608

Abstract

BACKGROUND

IgA nephropathy (IgAN) is characterized by deposition of polymers of IgA1 in the mesangium, accumulation of mesangial matrix and mesangial cell proliferation. Activation of the mesangial cell by IgA, via an IgA receptor, may be an initiating event in the pathology of IgAN.

METHODS

We examined the ability of radiolabeled, normal serum IgA1 to bind human mesangial cells (HMC). Activation of HMC by monomeric (mIgA1) and heat aggregated IgA1 (AIgA1) was compared by Northern analysis of c-jun expression. The expression of FcalphaR1 (CD89) mRNA on our cultured mesangial cells was also assessed by Northern analysis, reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry.

RESULTS

125I-mIgA1 and 125I-AIgA1 bound to HMC in a dose-dependent, saturable manner with similar affinities. There were 1.2 x 10(6) binding sites per cell, with an affinity constant of 2.3 x 10(6) M(-1). AIgA1 induced c-jun expression in a time and dose-dependent manner (2.4-fold above baseline after 60 min exposure to AIgA1 200 microg/ml) while mIgA1 had no effect on c-jun expression. No message for CD 89 was detectable in quiescent or AIgA1 stimulated HMC by Northern analysis or RT-PCR using several primer sequences based on the sequence of U937 FcalphaR cDNA. Flow cytometry on the mesangial cells, using My 43, a monoclonal antibody to FcalphaR1 confirmed that CD 89 was not present on the cell.

CONCLUSION

These results demonstrate that HMC bind mIgA1 and AIgA1 with similar affinity. However, activation of HMC requires an aggregated form of IgA1. These processes are independent of FcalphaR1, suggesting the presence of a new IgA receptor on mesangial cells.

摘要

背景

IgA 肾病（IgAN）的特征是 IgA1 聚合物在系膜中沉积、系膜基质积聚和系膜细胞增殖。IgA 通过 IgA 受体激活系膜细胞可能是 IgAN 病理过程中的起始事件。

方法

我们检测了放射性标记的正常血清 IgA1 与人系膜细胞（HMC）结合的能力。通过对 c-jun 表达的 Northern 分析比较单体 IgA1（mIgA1）和热聚集 IgA1（AIgA1）对 HMC 的激活作用。还通过 Northern 分析、逆转录聚合酶链反应（RT-PCR）和流式细胞术评估了我们培养的系膜细胞上 FcalphaR1（CD89）mRNA 的表达。

结果

125I-mIgA1 和 125I-AIgA1 以剂量依赖性、可饱和的方式与 HMC 结合，亲和力相似。每个细胞有 1.2×10^6 个结合位点，亲和常数为 2.3×10^6 M^-1。AIgA1 以时间和剂量依赖性方式诱导 c-jun 表达（暴露于 200μg/ml 的 AIgA1 60 分钟后比基线高 2.4 倍），而 mIgA1 对 c-jun 表达无影响。使用基于 U937 FcalphaR cDNA 序列的几种引物序列，通过 Northern 分析或 RT-PCR 在静止或 AIgA1 刺激的 HMC 中未检测到 CD89 的信息。使用针对 FcalphaR1 的单克隆抗体 My 43 对系膜细胞进行流式细胞术检测证实细胞上不存在 CD89。