Escherichia coli hemolysin and Staphylococcus aureas alpha-toxin potently induce neutrophil adhesion to cultured human endothelial cells.
Adhesion of polymorphonuclear leukocytes (PMN) to endothelial cells is an essential step in inflammatory reactions. We characterized the effects of two important bacterial exotoxins, Escherichia coli hemolysin (HlyA) and Staphylococcus aureus alpha-toxin (S. alpha-toxin) on PMN adhesion to cultured HUVEC. Both toxins increased adherence of human PMN to HUVEC in a dose- and time-dependent manner, peaking after 30 min at 0.01 hemolytic units/ml HlyA or 0.5 microg/ml S. alpha-toxin. Pretreatment of HUVEC with anti-P-selectin mAbs or of PMN with anti-CD11b/CD18 mAb reduced HlyA- and S. alpha-toxin-related cell adhesion significantly. Increased P-selectin expression on toxin-treated endothelial cells was demonstrated by cell surface ELISA. Compared with endotoxin, HlyA and S. alpha-toxin did not induce the expression of E-selectin, ICAM-1, or VCAM-1. FACS analysis showed increased CD11b/CD18 expression on HlyA-, but not on S. alpha-toxin-stimulated PMN. Platelet-activating factor, an important costimulatory factor for PMN adhesion and activation, was also active in the exotoxin-stimulated adhesion system, as evidenced by studies using the platelet-activating factor receptor antagonist BN50727. HPLC analysis of endothelial cell extracts confirmed enhanced toxin-mediated PAF synthesis. The capacity of exotoxins to stimulate PMN adhesion to endothelial cells may be relevant in patients with severe local or systemic bacterial infections.
Krüll
M
M
Department of Internal Medicine, Justus-Liebig University, Giessen, Germany.
Dold
C
C
Hippenstiel
S
S
Rosseau
S
S
Lohmeyer
J
J
Suttorp
N
N
D001381:Azepines / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D018821:CD18 Antigens / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis / Q000235:genetics; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013211:Staphylococcus aureus / Q000378:metabolism*; D058924:Thienopyridines; D014230:Triazoles / Q000494:pharmacology; D014471:Umbilical Veins
D001381:Azepines; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; C036507:Hlya protein, E coli; D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D058924:Thienopyridines; D014230:Triazoles; C039351:platelet activating factor receptor; C021091:staphylococcal alpha-toxin; C067429:Setipafant