EOSINOPHIL CHEMOTACTIC ACTIVITY IN BRONCHOALVEOLAR LAVAGE FROM IDIOPATHIC PULMONARY FIBROSIS IS DEPENDENT ON CYTOKINE PRIMING OF EOSINOPHILS

Increased numbers of eosinophils have been found in bronchoalveolar la vage (BAL) fluid obtained from patients with idiopathic pulmonary fibr osis (IPF), This suggests the presence of one or more cytokines in the lung tissue of patients with IPF, which are involved in the induction of migration of eosinophils towards the pulmonary compartment, To eva luate this hypothesis, we studied migratory responses of blood eosinop hils towards BAL fluid, Migratory responses were tested by means of a modified Boyden chamber assay in 21 patients with IPF and 14 healthy c ontrols, Experiments were performed with unprimed eosinophils and in v itro primed eosinophils (preincubated with 10(-11) M granulocyte macro phage-colony-stimulating factor). Changes in intracellular free Ca2+ ( [Ca2+](i)) in eosinophils in response to BAL fluid were also investiga ted, to characterize putative chemotaxins further, Chemotactic respons es of eosinophils were observed towards BAL fluid from both patients w ith IPF and controls, provided that the eosinophils were primed. No ch anges in [Ca3+](i) in eosinophils were detected in response to BAL flu id, Furthermore, neither a blocking antibody against interleukin-8 nor one against regulated on activation, normal T-cell, expressed and sec reted (RANTES) influenced the response. Since a chemotactic response o f in vitro primed eosinophils was also observed towards bronchoalveola r lavage fluid from normals, it was concluded, that in idiopathic pulm onary fibrosis, apart from the presence of a chemotactic factor in the lung tissue, other mechanisms such as priming of eosinophils in the p eripheral blood are responsible for the extravasation of eosinophils i nto the pulmonary compartment, As no changes in [Ca2+](i) were observe d in the eosinophils after incubation with bronchoalveolar lavage flui d, the chemotaxin responsible for the migratory responses is probably not one of the known eosinophil-activating chemokines.