Immunomodulatory activity of heparan sulfate mimetics from Escherichia coli K5 capsular polysaccharide in vitro

Carbohydr Polym. 2015 Jan 22:115:643-50. doi: 10.1016/j.carbpol.2014.08.119. Epub 2014 Sep 22.

Abstract

Escherichia coli K5 capsular polysaccharide (K5PS) has been used as starting material to synthesize heparan sulfate (HS) mimetics with various biological properties. This study determined the immunomodulatory activities of K5PS through the sulfation process. The immunomodulatory effects of sulfated K5 polysaccharide derivatives were evaluated in vitro on murine macrophages and lymphocytes. Results indicated that HS mimetics with high sulfation in the O-position stimulated cell proliferation of macrophages and lymphocytes, significantly enhanced cytokine secretion and upregulated the cytotoxicity of NK cells. This study suggests that high sulfation in O-position of HS is required for the immunomodulatory activities.

Keywords: Escherichia coli; Immunomodulatory activity; K5 capsular polysaccharide; Structure–activity correlation; Sulfation.

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Bacterial Capsules / chemistry*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytokines / immunology
  • Escherichia coli
  • Heparitin Sulfate
  • Immunoglobulin G / immunology
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • Mice, Inbred ICR
  • Spleen / cytology
  • Structure-Activity Relationship
  • Sulfates / chemistry
  • Sulfates / pharmacology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Cytokines
  • Immunoglobulin G
  • Immunologic Factors
  • Sulfates
  • capsular polysaccharide K5
  • Heparitin Sulfate