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 B4 (LTB4), and platelet-activating factor (PAF), to induce human eosinophils to migrate across 3.0-microns-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 > or = LTB4. However, their relative chemotactic potency through cellular barriers was different, with FMLP > LTB4 > 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, LTB4, 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Erger
R A
RA
Department of Internal Medicine, VA Medical Center, Iowa City, Iowa.
Casale
T B
TB
D000328:Adult; D002478:Cells, Cultured; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects*; D004847:Epithelial Cells; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D008168:Lung / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D014471:Umbilical Veins
D002631:Chemotactic Factors, Eosinophil; D010972:Platelet Activating Factor; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine