Effects of antirheumatic drugs on adhesiveness of endothelial cells and neutrophils.
Because disease-modifying antirheumatic drugs might exert part of their effects on adhesion of polymorphonuclear neutrophils (PMN) to endothelial cells, this being the first step for PMN migration to inflammatory lesions, we evaluated such drug effects in vitro. Gold sodium thiomalate (GSTM) impaired the ability of interleukin 1beta (IL-1beta)-stimulated human umbilical vein endothelial cells (HUVEC) to express E-selectin and to bind PMN but had no effect on the expression of intercellular adhesion molecule 1 (ICAM-1) or on hyperadhesivity of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMN. Auranofin (AF) interacted with HUVEC and PMN adhesiveness but in opposite directions: this drug hampered IL-1beta-induced HUVEC hyperadhesiveness and expression of E-selectin and intercellular adhesion molecule 1, but augmented PMN adherence and CD18 expression. The net effect of auranofin was a reduction of cytokine-driven adhesiveness and enhancement of formylpeptide-induced adhesion. Salazopyrin did not affect HUVEC or PMN adhesiveness or E-selectin and intercellular adhesion molecule 1 expression. Thus, the gold-containing drugs modulated HUVEC and PMN adhesiveness by different mechanisms but ones involving surface adhesion molecules.
Heimbürger
M
M
Department of Rheumatology, The Karolinska Institute at Huddinge University Hospital, Sweden. mikael.heimburger@rheum.hs.sll.se
Lerner
R
R
Palmblad
J
J
D018501:Antirheumatic Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012460:Sulfasalazine / Q000494:pharmacology*; D014471:Umbilical Veins