Degree of Neutrophil Chemotaxis Is Dependent upon the Chemoattractant and Barrier

Abstract

Stimulated neutrophil migration across lung endothelial and epithelial barriers is important in lung inflammatory processes. To better understand the interaction between chemoattractants, neutrophils, and endothelium and epithelium, we compared the ability of leukotriene B4 (LTB4), formylmethionylleucylphenylalanine (FMLP), and platelet-activating factor (PAF) to induce human neutrophil migration across 3-microns-pore filters alone and human umbilical vein endothelial (HUVE) cells and two different epithelial cell types, Madin-Darby canine kidney (MDCK) cells and human lung A549 cells, cultured in monolayers on these filters. LTB4, FMLP, and PAF induced neutrophil migration through naked filters, endothelial cells, and epithelial cells in a dose-related fashion. At optimal chemoattractant doses, LTB4, FMLP, and PAF induced relatively equivalent neutrophil migration through filters and endothelial and epithelial monolayers. However, the doses at which optimal neutrophil migration was observed to occur as well as the degree of neutrophil migration through the three barriers varied depending upon the chemoattractant. Based on dose-response experiments, the relative rank order of potency for the three chemoattractants was: LTB4 = FMLP greater than PAF for filter alone barrier; LTB4 greater than FMLP greater than PAF for HUVE cell barrier; and FMLP greater than LTB4 greater than PAF for MDCK and A549 epithelial cell barriers. Our data suggest that neutrophil chemotactic and subsequent lung inflammatory responses are interrelatedly influenced by both the quantity and type of chemoattractant present and the barrier through which the neutrophil must migrate.

Effect of Theophylline on Induced Sputum Inflammatory Indices and Neutrophil Chemotaxis in Chronic Obstructive Pulmonary Disease

“…However, neutrophils from patients with COPD may have reduced LTB 4 receptors, reduced LTB 4 response, or receptors that are blocked by prior LTB 4 release in vivo . In addition, the reduced response to LTB 4 may be due to the method used to assess chemotaxis, as previous studies have demonstrated that methodology can affect results (55,56). Several in vitro studies of the effect of theophylline demonstrate a similar reduction in neutrophil chemotaxis (57,58), although this is dependent on the dose used (59).…”

lnterleukin-8 in Airway Inflammation in Patients with Asthma and Chronic Obstructive Pulmonary Disease

“…These include leukotriene B., [8], platelet-activating factor KARGER I -Mail kargem»kargcr.ch l'a\ • 41 61 306 12 34 [9] and a product of the complement pathway C5a [10]. Among these factors IL-8 is particularly of interest because it is resistant to many denaturating treatments, like oxida tion or hydrolysis [11], and is known to persist in its active form in tissues for long periods [12].…”

Factors influencing airway inflammation in chronic obstructive pulmonary disease

“…There are a number of other chemoattractants that could play a role in the airways including C5a generated from complement activation46; modified AAT47; leucocyte elastase-inhibitor complexes48; protein and peptide components of damaged extracellular matrix such as collagen,49 elastin50 and laminin51; antigen-antibody complexes52; bacterial factors including the formyl peptides such as fMLP53 and lipopolysaccharide or endotoxin which can prime neutrophil functions including the chemotactic responses 54…”