MECHANISMS INVOLVED IN EOSINOPHIL MIGRATION - PLATELET-ACTIVATING FACTOR-INDUCED CHEMOTAXIS AND INTERLEUKIN-5-INDUCED CHEMOKINESIS ARE MEDIATED BY DIFFERENT SIGNALS

Eosinophils play an important role in the pathogenesis of allergic dis eases such as allergic asthma, Eosinophil migration in vitro can be di vided into directed migration, or chemotaxis, and random migration, or chemokinesis. Here, we studied intracellular signals involved in eosi nophil migration in vitro induced by platelet-activating factor (PAF) and interleukin-5 (IL-5), applying a Boyden chamber assay, Migration i nduced by PAF (10(-11)-10(-6) M) largely consisted of chemotaxis with some chemokinesis, whereas IL-5 (10(-12)-10(-8) M) induced chemokinesi s only, Eosinophils were depleted from intracellular and extracellular Ca2+ to study the role of Ca2+ as a second messenger, Ca2+ depletion did not change PAF-induced chemotaxis, however, IL-5-induced chemokine sis was inhibited, Interestingly, PAF, but not IL-5, induced changes i n [Ca2+](i). This rise originated mainly from internal stores, Inhibit ion of protein kinase A by H-89 and protein kinase C by GF 109203X had no effect on both forms of eosinophil migration, Addition of the prot ein kinase inhibitor staurosporine significantly inhibited IL-5-induce d chemokinesis, Inhibition of tyrosine kinases by herbimycin A complet ely blocked IL-5-induced chemokinesis, PAF and IL-5-induced actin poly merization was studied to compare migratory responses with a migration -associated intracellular response. Ca2+ depletion significantly enhan ced PAF-induced (10(-8) M) actin polymerization, whereas IL-5-induced actin polymerization was not influenced, Addition of staurosporine led to an increase in F-actin, Subsequent addition of PAF or IL-5 resulte d in an additive increase in F-actin content. In summary, both forms o f eosinophil migration are protein kinase A and protein kinase C indep endent, In contrast to PAF-induced chemotaxis, IL-5-induced chemokines is was found to be completely Ca2+ and tyrosine kinase dependent.