Eotaxin promotes eosinophil transmigration via the activation of the plasminogen-plasmin system

The effect of eotaxin, a potent eosinophil chemotactic factor, on eosinophi l transmigration through a reconstituted basal membrane (Matrigel (R)) was evaluated. Eotaxin induced significant eosinophil transmigration in the pre sence of 10% fetal bovine serum (FBS) and interleukin-5, Its effect was opt imal at 0.01 muM, and it plateaued at 18 h. Eotaxin's effect was greater wi th eosinophils from asthmatic subjects (61.1 +/- 3.4%) than with eosinophil s from normal subjects (38.1 +/- 4.2%) (P < 0.001). Inhibition of metallopr oteinases decreased eotaxin-induced transmigration by less than or equal to 10.4 %, whereas inhibition of the plasminogen-plasmin system decreased eot axin's effect by less than or equal to 44.4% (P = 0.0002), Moreover, eotaxi n-induced transmigration was largely diminished in medium with low concentr ations 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 wit h cells from asthmatics than with normal cells, and that its effect depends predominantly on the activation of the plasminogen-plasmin system.