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Mechanisms involved in eosinophil migration. Platelet‐activating factor‐induced Chemotaxis and interleukin‐5‐induced chemokinesis are mediated by different signals
Author(s) -
Schweizer René C.,
KesselWelmers Berns A. C.,
Warringa Ruud A. J.,
Maikoe Tjander,
Raaijmakers Jan A. M.,
Lammers JanWillem J.,
Koenderman Leo
Publication year - 1996
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.59.3.347
Subject(s) - chemokinesis , chemotaxis , staurosporine , microbiology and biotechnology , biology , platelet activating factor , protein kinase c , eosinophil , immunology , signal transduction , biochemistry , receptor , asthma
Eosinophils play an important role in the pathogenesis of allergic diseases such as allergic asthma. Eosinophil migration in vitro can be divided into directed migration, or Chemotaxis, and random migration, or chemokinesis. Here, we studied intracellular signals involved in eosinophil migration in vitro induced by platelet‐activating factor (PAF) and interleukin‐5 (IL‐5), applying a Boyden chamber assay. Migration induced by PAF (10 ‐11 ‐10 ‐6 M) largely consisted of Chemotaxis with some chemokinesis, whereas IL‐5 (10 ‐12 ‐10 ‐8 M) induced chemokinesis only. Eosinophils were depleted from intracellular and extracellular Ca 2+ to study the role of Ca 2+ as a second messenger. Ca 2+ depletion did not change PAF‐induced Chemotaxis, however, IL‐5‐induced chemokinesis was inhibited. Interestingly, PAF, but not IL‐5, induced changes in [Ca 2+ ] i . This rise originated mainly from internal stores. Inhibition 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 protein kinase inhibitor staurosporine significantly inhibited IL‐5‐induced chemokinesis. Inhibition of tyrosine kinases by herbimycin A completely blocked IL‐5‐induced chemokinesis. PAF and IL‐5‐induced actin polymerization was studied to compare migratory responses with a migration‐associated intracellular response. Ca 2+ depletion significantly enhanced 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 resulted in an additive increase in F‐actin content. In summary, both forms of eosinophil migration are protein kinase A and protein kinase C independent. In contrast to PAF‐induced Chemotaxis, IL‐5‐induced chemokinesis was found to be completely Ca 2+ and tyrosine kinase dependent.