Characterization of a neutrophil cell surface glycosaminoglycan that mediates binding of platelet factor 4

被引:93
作者
Petersen, F
Brandt, E
Lindahl, U
Spillmann, D
机构
[1] Univ Uppsala, Ctr Biomed, Dept Med Biochem & Microbiol, S-75123 Uppsala, Sweden
[2] Res Ctr Borstel, Dept Immunol & Cell Biol, D-23845 Borstel, Germany
关键词
D O I
10.1074/jbc.274.18.12376
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Platelet factor 4 (PF-4) is a platelet-derived alpha-chemokine that binds to and activates human neutrophils to undergo specific functions like exocytosis or adhesion. PF-4 binding has been shown to be independent of interleukin-8 receptors and could be inhibited by soluble chondroitin sulfate type glycosaminoglycans or by pretreatment of cells with chondroitinase ABC. Here we present evidence that surface-expressed neutrophil glycosaminoglycans are of chondroitin sulfate type and that this species binds to the tetrameric form of PF-4, The glycosaminoglycans consist of a single type of chain with an average molecular mass of similar to 23 kDa and are composed of similar to 85-90% chondroitin 8-sulfate disaccharide units type CSA (-->4GlcA beta 1-->3GalNAc(4-O-sulfate)beta 1-->) and of similar to 10-15% di-O-sulfated disaccharide units. A major part of these di-O-sulfated disaccharide units are CSE units (-->4GlcA beta 1-->3GaLNAc(4,6-O-sulfate)beta 1-->). Binding studies revealed that the interaction of chondroitin sulfate with PF-4 required at least 20 monosaccharide units for significant binding. The di-O-sulfated disaccharide units in neutrophil glycosaminoglycans clearly promoted the affinity to PF-4, which showed a K-d similar to 0.8 mu M as the affinities of bovine cartilage chondroitin sulfate A, porcine skin dermatan sulfate, or bovine cartilage chondroitin sulfate C, all consisting exclusively of monosulfated disaccharide units, were found to be 3-5-fold lower. Taken together, our data indicate that chondroitin sulfate chains function as physiologically relevant binding sites for PF-4 on neutrophils and that the affinity of these chains for PF-4 is controlled by their degree of sulfation.
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页码:12376 / 12382
页数:7
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