Binding of polymeric IgG to fibronectin in extracellular matrices: an in vitro paradigm for immune-complex deposition.
Binding of polymeric IgG to fibronectin in extracellular matrices: an in vitro paradigm for immune-complex deposition.
复制标题
聚合 IgG 与细胞外基质中纤连蛋白的结合:免疫复合物沉积的体外范例。
DOI:
10.1016/s0161-5890(02)00040-8
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发表时间:
2002
影响因子:
3.6
通讯作者:
Gold,LeslieI
中科院分区:
文献类型:
--
作者:
Rostagno,AguedaA;Gallo,Gloria;Gold,LeslieI
We have previously shown a biochemical interaction between fibronectin (Fn) and polymeric immunoglobulins (Igs), that we localized to the fourth and fifth N-terminal type I repeats (4F 1 ·5F 1 ) in Fn and the Fc portion of IgG. Therefore, we hypothesized that Fn, as a constituent of the extracellular matrix (ECM) may directly bind circulating immune complexes (ICs) causing their deposition, thereby contributing to the pathogenesis of IC diseases. As an in vitro paradigm to test this idea, we have generated Fn-containing ECMs from varied cells in culture and demonstrated a saturable dose-dependent binding of aggregated (agg) IgG, as a prototype of ICs, as well as the binding of both heat and cold aggregated purified type I cryoglobulins (CGs) to these ECMs. No binding was observed to ECMs (Matrigel) that do not contain Fn. Characteristic of our previous findings, polymeric but not monomeric IgG bound to the acellular Fn-containing ECMs. To further demonstrate the specificity of the interaction and implicate matrix Fn in the binding of aggIgG, complete inhibition of binding of aggIgG to Fn was achieved by blocking Fn on the ECMs with anti-Fn antiserum and by preincubation of the Ig aggregates with anti-human IgG antibodies. By competing the binding interaction with fluid phase Fn and the Ig-binding site on Fn,4F1·5F1, 70% inhibition was obtained. Additional experiments performed with purified CGs show that an identical dose-dependent increase in Fn binding occurred using both preformed and forming cryoprecipitates suggesting that Fn does not confer cryoprecipitation of CGs and that the specific association of Fn with cryoprecipitates probably results from their polymeric configuration. Our results support the notion that Fn, as it exits in expanding ECMs characteristic of glomerulonephropathies and rheumatoid synovial disease, specifically interacts with complexed/polymeric Igs, thereby perpetuating IC deposition and playing a role in the pathogenesis of IC diseases.
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影响因子:
13.6
作者:
S. Waga;K. Sugimoto;Hiroshi Tanaka;Tatsuo Ito;T. Nakahata;T. Tateyama;Y. Kakizaki;Masaru Yokoyama
通讯作者:
Masaru Yokoyama
影响因子:
4.6
作者:
D. Brandau;R. O’Donnell;V. L. KIMMEL‐TRUITT
通讯作者:
V. L. KIMMEL‐TRUITT
影响因子:
2.4
作者:
M. Villar;F. García‐Bragado;J. Joven;M. Biosca;M. Antolín;M. Rodrigo;S. Schwartz
通讯作者:
S. Schwartz
影响因子:
7.5
作者:
POTTS, JR;CAMPBELL, ID
通讯作者:
CAMPBELL, ID
DOI:
10.1073/pnas.85.13.4865
发表时间:
1988-07-01
影响因子:
11.1
作者:
CEDERHOLM, B;WIESLANDER, J;HEINEGARD, D
通讯作者:
HEINEGARD, D