Eotaxin promotes eosinophil transmigration via the activation of the plasminogen-plasmin system.
The effect of eotaxin, a potent eosinophil chemotactic factor, on eosinophil transmigration through a reconstituted basal membrane (Matrigel) was evaluated. Eotaxin induced significant eosinophil transmigration in the presence of 10% fetal bovine serum (FBS) and interleukin-5. Its effect was optimal at 0.01 microM, and it plateaued at 18 h. Eotaxin's effect was greater with eosinophils from asthmatic subjects (61.1 +/- 3.4%) than with eosinophils from normal subjects (38.7 +/- 4.2%) (P < 0.001). Inhibition of metalloproteinases decreased eotaxin-induced transmigration by < or = 10.4%, whereas inhibition of the plasminogen-plasmin system decreased eotaxin's effect by < or = 44.4% (P = 0.0002). Moreover, eotaxin-induced transmigration was largely diminished in medium with low concentrations of serum [0.5% FBS: 6.1 +/- 2.4%; 10% FBS: 40.2 +/- 5.8% (P = 0.0001)] but returned to its initial level with the addition of plasminogen (2 U/mL) to 0.5% FBS (43.1 +/- 6.5%). These data show that eotaxin is an efficient promoter of eosinophil transmigration in vitro, that it is more potent with cells from asthmatics than with normal cells, and that its effect depends predominantly on the activation of the plasminogen-plasmin system.
Ferland
C
C
Unité de Recherche en Pneumologie, Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et Pneumologie de l'Université, Laval, Quebec, Canada.
Guilbert
M
M
Davoine
F
F
Flamand
N
N
Chakir
J
J
Laviolette
M
M
D000328:Adult; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001249:Asthma / Q000097:blood*; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism* / Q000494:pharmacology; D003094:Collagen; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004789:Enzyme Activation; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007700:Kinetics; D007797:Laminin; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D010958:Plasminogen / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology; D011509:Proteoglycans; D054397:Receptors, CCR3; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis; D055293:Receptors, Urokinase Plasminogen Activator
D001095:Arachidonic Acids; C108282:BB 3103; C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D004338:Drug Combinations; D006877:Hydroxamic Acids; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; C524898:PLAUR protein, human; D010972:Platelet Activating Factor; D011509:Proteoglycans; D054397:Receptors, CCR3; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D055293:Receptors, Urokinase Plasminogen Activator; C059485:matrigel; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D010958:Plasminogen; D003094:Collagen; D005341:Fibrinolysin