title: Neutrophil migration in opposing chemoattractant gradients using microfluidic chemotaxis devices.
abstract: Neutrophils migrating in tissue respond to complex overlapping signals generated by a variety of chemotactic factors (CFs). Previous studies suggested a hierarchy between bacteria-derived CFs and host-derived CFs but could not differentiate neutrophil response to potentially equal host-derived CFs (IL-8 and LTB4). This paper reports neutrophil migration in conflicting gradients of IL-8 and LTB4 using a microfluidic chemotaxis device that can generate stable and well-defined gradients. We quantitatively characterized the movement of cells from time-lapse images. Neutrophils migrate more efficiently toward single IL-8 gradients than single LTB4 gradients as measured by the effective chemotactic index (ECI). In opposing gradients of IL-8 and LTB4, neutrophils show obvious chemotaxis toward a distant gradient, consistent with previous reports. When an opposing gradient of LTB4 is present, neutrophils show less effective chemotaxis toward IL-8 than when they are in a gradient of IL-8 alone. In contrast, the chemotactic response of neutrophils to LTB4 is not reduced in opposing gradients as compared to that in a single LTB4 gradient. These results indicate that the presence of one host-derived CF modifies the response of neutrophils to a second CF suggesting a subtle hierarchy between them.
authors.affiliation: Department of Physics and Astronomy, University of California at Irvine, Irvine, CA 92697, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Lin
authors.forename: Connie Minh-Canh
authors.initials: CM
authors.lastname: Nguyen
authors.forename: Shur-Jen
authors.initials: SJ
authors.lastname: Wang
authors.forename: Wajeeh
authors.initials: W
authors.lastname: Saadi
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gross
authors.forename: Noo Li
authors.initials: NL
authors.lastname: Jeon
mesh_terms: D018929:Cell Culture Techniques / Q000295:instrumentation; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000494:pharmacology*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
chemical_list: D002630:Chemotactic Factors; D004338:Drug Combinations; D016209:Interleukin-8; D007975:Leukotriene B4