title: Transmigration of eosinophils through basement membrane components in vitro: synergistic effects of platelet-activating factor and eosinophil-active cytokines.
abstract: Migration of eosinophils through the basement membrane barrier is an important step for their infiltration into tissues. To investigate the mechanism of transmigration, we used a chamber fitted with a Matrigel membrane as a model of the basement membrane. In this model, eosinophils treated with cytokines or chemotactic factors alone did not transmigrate from the upper to the lower chamber. However, platelet-activating factor (PAF) strongly induced transmigration of eosinophils stimulated by interleukin (IL)-5, indicating that both a cytokine and a chemotactic factor are required for eosinophil migration through Matrigel. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3 also stimulated eosinophil transmigration in the presence of PAF. Of seven eosinophil chemotactic factors tested, leukotriene B4, C5a, RANTES, macrophage inflammatory protein-1alpha, and IL-8 did not induce significant eosinophil transmigration. Only PAF and eotaxin induced transmigration of eosinophils through Matrigel in the presence of IL-5; PAF was more potent than eotaxin at the optimal concentration. In contrast, PAF, eotaxin, and RANTES all potently induced migration of eosinophils through bare membrane in the absence of IL-5. Finally, eosinophil migration through Matrigel was markedly reduced by a combination of anti-CD18 and anti-CD29 monoclonal antibodies, suggesting that it is mediated by beta1- and beta2-integrin adhesion molecules. Our findings demonstrate that eosinophil transmigration through a basement membrane model requires both a specific chemoattractant, such as PAF, and an eosinophil-activating cytokine, such as IL-5. This synergistic effect is likely important in the tissue accumulation of activated eosinophils in allergic and other eosinophil-associated diseases.
authors.affiliation: Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Kita
authors.forename: T J
authors.initials: TJ
authors.lastname: George
authors.forename: G J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: K M
authors.initials: KM
authors.lastname: Leiferman
mesh_terms: D001485:Basement Membrane / Q000166:cytology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003094:Collagen; D016207:Cytokines / Q000494:pharmacology*; D004338:Drug Combinations; D004804:Eosinophils / Q000166:cytology*; D006801:Humans; D007700:Kinetics; D007797:Laminin; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011509:Proteoglycans
chemical_list: D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D016207:Cytokines; D004338:Drug Combinations; D007797:Laminin; D010972:Platelet Activating Factor; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen