Mechanisms involved in eosinophil migration. Platelet-activating factor-induced Chemotaxis and interleukin-5-induced chemokinesis are mediated by different signals

Abstract

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 Ca2+ to study the role of Ca2+ as a second messenger. Ca2+ depletion did not change PAF-induced chemotaxis, however, IL-5-induced chemokinesis was inhibited. Interestingly, PAF, but not IL-5, induced changes in [Ca2+]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. Ca2+ 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 Ca2+ and tyrosine kinase dependent.

Plasminogen Is an Important Regulator in the Pathogenesis of a Murine Model of Asthma

“…For example, the urokinase plasminogen activator (uPA)/plasminogen have been implicated in the extravasation of T cells and the uPA receptor was identified as a Tlymphocyte activation antigen (34). A variety of agonists (35)(36)(37) induce uPA-dependent plasminogen activation of eosinophils. Also, inhibition of uPA, MMPs, or Plg/plasmin decreases in vitro eosinophil adhesion (38) or transmigration (12,37).…”

Major basic protein, but not eosinophil cationic protein or eosinophil protein X, is related to atopy in cystic fibrosis

“…One putative principle involved in the priming of eosinophils is interleukin (IL)-5, as has been demonstrated in vitro and in vivo for bronchial asthma (20).…”

Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1 synthesis by human neutrophils

“…HUVECs were isolated from human umbilical cord veins as described previously [29]. The cells were cultured in endothelial cell growth medium-2 (Lonza, Walkersville, MD, USA).…”