Endotoxin and muramyl dipeptide modulate surface receptor expression on human mononuclear cells

Immunopharmacology. 2000 Jul 20;48(2):117-28. doi: 10.1016/s0162-3109(00)00195-8.

Abstract

Endotoxin (lipopolysaccharide (LPS), 100 ng/ml) and muramyl dipeptide (MDP 100 ng/ml), two immunomodulatory bacterial cell wall products, were incubated with human whole blood, and the expression of receptors involved in antigen presentation, costimulation, and cell activation was investigated by use of flow cytometry. On monocytes, LPS and MDP increased surface expression of human leukocyte antigen-DR (HLA-DR), CD18, CD54 (intercellular adhesion molecule-1, ICAM-1), and CD86 (B7-2). On lymphocytes, LPS but not MDP increased HLA-DR expression after 18 h. The expression of CD28, CD49d/CD29, and CD106 (vascular cell adhesion molecule-1, VCAM-1) remained unchanged on both monocytes and lymphocytes. The early increase (1-6 h) of CD18 and ICAM-1 expression led us to hypothesize that CD18-dependent costimulatory signals were involved in the later (6 h) increase of monocyte HLA-DR expression. However, blocking studies using monoclonal antibodies against CD18 (IB4, 15 microg/ml) demonstrated that the LPS- and MDP-induced increase of HLA-DR and ICAM-1 expression on monocytes was not mediated through CD18. LPS induced the expression of the early activation marker CD69 by a CD14-dependent but CD18-independent mechanism, whereas MDP did not induce CD69 expression. Analysis of leukocyte subsets demonstrated that CD4(+) T-cells, CD8(+) T-cell, CD19(+) B-cells, CD56(+) natural killer (NK)-cells, and CD14(+) monocytes increased the expression of CD69 after stimulation with LPS. Collectively, these data demonstrate a stronger immunomodulatory effect of LPS compared with MDP which may, in part, explain the established difference of toxicity between these two bacterial cell wall products.

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology*
  • Adjuvants, Immunologic / pharmacology*
  • Antigens, CD / biosynthesis
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • B7-2 Antigen
  • CD18 Antigens / biosynthesis
  • CD18 Antigens / metabolism
  • Cells, Cultured
  • Flow Cytometry
  • HLA-DR Antigens / biosynthesis
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Lectins, C-Type
  • Lipopolysaccharides / pharmacology*
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / metabolism
  • Monocytes / immunology*
  • Monocytes / metabolism*
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / metabolism
  • Time Factors

Substances

  • Adjuvants, Immunologic
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • B7-2 Antigen
  • CD18 Antigens
  • CD69 antigen
  • CD86 protein, human
  • HLA-DR Antigens
  • Lectins, C-Type
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Intercellular Adhesion Molecule-1
  • Acetylmuramyl-Alanyl-Isoglutamine