摘要：

Heparin is known to influence the growth, proliferation, and migration of vascular cells, but the precise mechanisms are unknown. We previously demonstrated that unfractionated heparin (UH) binds to the platelet integrin αIIbβ3, and enhances ligand binding. To help define the specificity and site(s) of heparin-integrin interactions, we employed the erythroleukemic K562 cell line, transfected to express specific integrins (αvβ3, αvβ5, and αIIbβ3). By comparing K562 cells expressing a common α subunit (Kαvβ3, Kαvβ5) with cells expressing a common β subunit (Kαvβ3, KαIIbβ3), we observed that heparin differentially modulated integrin-mediated adhesion to vitronectin. UH at 0.5–7.5 μg/ml consistently enhanced the adhesion of β3expressing cells (Kαvβ3,KαIIbβ3). In contrast, UH at 0.5–7.5 μg/ml inhibited Kαvβ5adhesion. Experiments using integrin-blocking antibodies, appropriate control ligands, and nontransfected native K562 cells revealed that heparin's actions were mediated by the specific integrins under study. Preincubation of heparin with Kαvβ3cells enhanced adhesion, while preincubation of heparin with the adhesive substrate (vitronectin) had minimal effect. There was a structural specificity to heparin's effect, in that a low molecular weight heparin and chondroitin sulfate showed significantly less enhancement of adhesion. These findings suggest that heparin's modulation of integrin-ligand interactions occurs through its action on the integrin. The inhibitory or stimulatory effects of heparin depend on the β subunit type, and the potency is dictated by structural characteristics of the glycosaminoglycan.

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