Impairment of selectin-mediated leukocyte adhesion to venular endothelium in spontaneously hypertensive rats

Makoto Suematsu, Hidekazu Suzuki, Takuya Tamatani, Yutaka Iigou, Frank A. DeLano, Masayuki Miyasaka, Michael J. Forrest, Reiji Kannagi, Benjamin W. Zweifach, Yuzuru Ishimura, Geert W. Schmid-Schönbein

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Abstract

The present study was designed to elucidate whether molecular mechanisms for leukocyte adhesion to microvascular endothelium may differ between spontaneously hypertensive rats and Wistar Kyoto rats. Leukocyte rolling and adhesion were investigated while monitoring venular wall shear rates in the mesenteric microcirculation stimulated with histamine or tert-butyl hydroperoxide in the two strains. In Wistar Kyoto rats, 10 μM histamine as well as 500 μM tert-butyl hydroperoxide promoted a significant reduction of venular leukocyte rolling velocity and subsequent adhesion. These changes in leukocyte behavior were blocked by monoclonal antibodies against P-selectin (PB 1.3) and against sialyl Lewis X-like carbohydrates (2H5). However, spontaneously hypertensive rats exhibited a blunted response of the stimulus- elicited leukocyte rolling, which was associated with impairment of venular P-selectin expression as well as s decrease in the expression of sialyl Lewis X-like carbohydrates on circulating neutrophils. No significant differences were detected between the two strains not only in the surface CD11b/CD18 expression but also in the CD18-mediated adhesivity of neutrophils to intracellular adhesion molecule-1 transfectants in vitro. These results suggest that impairment of selectin-mediated leukocyte adhesion is an event responsible for disorders of inflammatory responses in spontaneously hypertensive rats.

Original languageEnglish
Pages (from-to)2009-2016
Number of pages8
JournalJournal of Clinical Investigation
Volume96
Issue number4
DOIs
Publication statusPublished - 1995 Oct

Keywords

  • P-selectin
  • endothelial cells
  • hypertension
  • leukocyte adhesion
  • sialyl Lewis X

ASJC Scopus subject areas

  • Medicine(all)

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    Suematsu, M., Suzuki, H., Tamatani, T., Iigou, Y., DeLano, F. A., Miyasaka, M., Forrest, M. J., Kannagi, R., Zweifach, B. W., Ishimura, Y., & Schmid-Schönbein, G. W. (1995). Impairment of selectin-mediated leukocyte adhesion to venular endothelium in spontaneously hypertensive rats. Journal of Clinical Investigation, 96(4), 2009-2016. https://doi.org/10.1172/JCI118248