Immunoneutralization of glycoprotein Ibα attenuates endotoxin-induced interactions of platelets and leukocytes with rat venular endothelium in vivo

Tomihiro Katayama, Yasuo Ikeda, Makoto Handa, Takuya Tamatani, Shinji Sakamoto, Masaharu Ito, Yuzuru Ishimura, Makoto Suematsu

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

This study aimed to examine molecular mechanisms for endotoxin-induced adhesive changes in platelets in vivo. Platelets labeled with carboxyfluorescein diacetate succinimidyl ester were visualized in rat roesenteric venules through intravital microscopy assisted by a high-speed fluorescence video imager at 1000 frames per second or by a normal-speed intensifier under monitoring of erythrocyte velocity. Leukocyte rolling was examined by normal-speed transmission video images. The velocity of platelets traveling along the centerline of venules followed that of erythrocytes, whereas that measured at the periendothelial space was significantly smaller than the erythrocyte velocity; a majority of these cells exhibited transient but notable rolling with endothelium. Administration of endotoxin increased the density of periendothelial platelets and reduced the rolling velocities of platelets and leukocytes in venules: All events were attenuated by anti- rat P-selectin monoclonal antibody s789G or by anti-human glycoprotein (GP) Ibα monoclonal antibody GUR83/35, which blocks ristocetin-induced aggregation of rat platelets. Isolated rat platelets injected into endotoxin- pretreated rats were able to roll on the venules. This event was attenuated by pretreatment of platelets in vitro with GUR83/35 but not with s789G, suggesting involvement of endothelial P-selectin and platelet GP Ibα in the endotoxin-induced responses. Furthermore, isolated human platelets showed similar rolling interactions with endotoxin-preexposed rat venules, and pretreatment of the platelets with GUR83/35, but not with s789G, significantly reduced such interactions. Our results provide the first evidence for involvement of GP Ibα in endotoxin-induced microvascular rolling of platelets and leukocytes, and this system serves as a potentially useful tool to examine GP Ibα-associated function of human platelets in vivo.

Original languageEnglish
Pages (from-to)1031-1037
Number of pages7
JournalCirculation research
Volume86
Issue number10
DOIs
Publication statusPublished - 2000 May 26

Keywords

  • Endothelial cells
  • Endotoxin
  • P-selectin
  • Platelets
  • Shear stress

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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