Interaction of human plasminogen kringles 1-3 (angiostatin) with human umbilical vein endothelial cells (huvec): binding properties and effects on cell proliferation


Journal Article

Receptors which bind plasminogen (Pg) have previously been demonstrated in HUVEC. To determine whether the mechanism by which the Pg fragment, angiostatin, inhibits endothelial cell migralion and/or proliferation involves interaction with the Pg receptor, we have performed experiments to analyze the effect of PgKl-3 on binding of intact Pg lo endothelial cells. Intact Pg isoforms I and 2 bind to HUVEC in a concentration-dependent, saturable manner. Binding of both Pgl and Pg2 is inhibited by 6aminohexanioc acid (6-AHA) (60% and 75%). The K1-3 fragment derived from either Pgl or Pg2 also bound to HUVEC in a concentration-dependent, saturable manner, l n contrast to data observed with intact Pg, binding of Pgl K1-3 and Pg2Kl-3 was not dramatically inhibited by 6-AHA (15% and 18%) or benzamidine, suggesting that binding of Pg derived kringles to HUVEC is not primarily lysine binding site dependent. Lack of competition by L-lactose and 3-N-acetylneuramin-lactose suggested that the carbohydrate chain is not responsible for binding to HUVEC. To study the effect of Pg and PgKl-3 on endothelial cell proliferation, incorporation of BrdU was determined. A cytostatic effect was observed with both Pgl and Pg2 (93% and 96%) as well as PglKI-3 and Pg2Kl-3 (68% and 47%). To determine whether PgKl-3 binds to the same site on HUVEC as intact Pg, binding to biotin labelled HUVEC membrane extracts was analyzed. PgKl-3 did not interact with the Pg binding protein suggesting that angiostatin binds to an alternative site on HUVEC and may influence cell proliferation.

Full Text

Duke Authors

Cited Authors

  • Moser, TL; Stack, MS; Gonzalez-Gronow, M; Pizzo, SV

Published Date

  • January 1, 1996

Published In

Volume / Issue

  • 10 / SUPPL. 3

Start / End Page

  • 73 -

International Standard Serial Number (ISSN)

  • 0268-9499

Digital Object Identifier (DOI)

  • 10.1016/s0268-9499(96)80336-5

Citation Source

  • Scopus