The effects of the potent glucocorticoid budesonide on adhesion of eosinophils to human vascular endothelial cells and on endothelial expression of adhesion molecules.
An important early event in the formation of the allergic late-phase cellular infiltrate is the adhesion of eosinophils to vascular endothelium. Because glucocorticoids are potent inhibitors of this late-phase inflammatory reaction, we examined the effect of the glucocorticoid budesonide on in vitro adhesion of human eosinophils to cultured human umbilical vein endothelial cells (HUVEC). Pretreatment of eosinophils, HUVEC or both with budesonide (10(-7) M) did not inhibit either baseline adhesion or that stimulated by interleukin-1 beta (50 U/ml, 4 hr) or interleukin-4 (100 U/ml, 21-23 hr) or the leukocyte activators N-formyl-methionyl-leucyl-phenylalanine (10(-6) M, 10 min) or platelet-activating factor (10(-6) M, 10 min). Pretreatment of HUVEC with budesonide also failed to affect expression of the adhesion molecules E-selectin, intercellular adhesion molecule-1, or vascular cell adhesion molecule-1 on resting HUVEC or after stimulation with interleukin-1 beta (10 U/ml, 4 hr), tumor necrosis factor (6 U/ml, 4 hr) or interleukin-4 (50 U/ml, 24 hr). Because budesonide failed to inhibit stimulus-induced eosinophil adhesion responses or endothelial adhesion molecule expression, we speculate that glucocorticoids inhibit the formation of eosinophil-enriched tissue infiltrates by inhibiting the production rather than the activity of eosinophil- or endothelial-activating factors or by altering the survival of eosinophils in tissues.
Kaiser
J
J
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland.
Bickel
C A
CA
Bochner
B S
BS
Schleimer
R P
RP
D019819:Budesonide; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011282:Pregnenediones / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D010972:Platelet Activating Factor; D011282:Pregnenediones; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019819:Budesonide; D009240:N-Formylmethionine Leucyl-Phenylalanine