COMPARATIVE-STUDIES INDICATE THAT PLATELET-ACTIVATING-FACTOR IS A RELATIVELY WEAK EOSINOPHILOTACTIC MEDIATOR

Eosinophils are important immune effector cells in a variety of allergic responses and inflammatory lung diseases. Bacterial products and inflammatory mediators have been implicated in inducing an influx of eosinophils into the respiratory tract subsequent to an acute inflammatory response. Therefore, to better understand the role of eosinophils in lung inflammation, we compared the ability of three known chemoattractants, formylmethionylleucylphenylalanine (FMLP), leukotriene B-4 (LTB(4)), and platelet-activating factor (PAF), to induce human eosinophils to migrate across 3.0-mu m-pore naked filters and human umbilical vein endothelial cells (HUVEC) and A549 human pulmonary type II-like epithelial (A549) cells cultured in monolayers on these filters. Kinetic experiments indicated that eosinophil migration through all three barriers occurred by 60 min and plateaued by 2 h. Each of these chemoattractants induced eosinophil migration in dose-responsive fashion across all three barriers. Although similar maximal eosinophil migration was observed, the doses at which this occurred varied, indicating that the rank order of potency through naked filters is FMLP > PAF greater than or equal to LTB(4). However, their relative chemotactic potency through cellular barriers was different, with FMLP > LTB(4) > PAF In contrast to previous studies with neutrophils, the rank order of potency of the three chemoattractants was not influenced by the barrier through which the eosinophil migrated. Thus, these and previous data show that FMLP, LTB(4), and PAF are eosinophil and neutrophil chemoattractants. Therefore, it is likely that these three agents are important mediators of granulocytic inflammatory responses in the lung, albeit with different potency profiles. Indeed, the contributions of PAF to granulocyte, and especially eosinophil, inflammatory responses may not be as significant as previously postulated since it is a relatively weak chemoattractant in direct comparative studies.