title: Soluble vascular cell adhesion molecule (VCAM)-Fc fusion protein induces leukotriene C4 secretion in platelet-activating factor-stimulated eosinophils.
abstract: Eosinophil adhesion to vascular cell adhesion molecule-1 (VCAM-1) is important for cellular recruitment into allergic inflammatory sites. To determine whether eosinophil adhesion to VCAM-1 affects cell function, leukotriene C4 (LTC4) was measured. Human eosinophils were incubated with platelet-activating factor (PAF) in the presence or absence of soluble VCAM-Fc fusion protein (sVCAM-Fc) or immobilized VCAM-Fc. sVCAM-Fc induced a concentration-dependent increase in LTC4 secretion, which was dependent on the presence of PAF and not blocked by cyclic peptides shown to inhibit alpha4beta1-dependent adhesion. Likewise, soluble ICAM-Fc induced a concentration-dependent LTC4 secretion. LTC4 secretion was induced by the calcium ionophore, A23187, and the combination of sVCAM-Fc and A23187 had synergistic properties. It is interesting to note that Mn2+ or anti-beta1 monoclonal antibody, TS2/16, inhibited LTC4 secretion induced by sVCAM-Fc and PAF. Eosinophil adhesion to VCAM-Fc or interleukin-1 beta-stimulated endothelial cells did not induce LTC4 secretion. These data suggest that sVCAM-Fc-induced LTC4 secretion depends on distinct signals from those of eosinophil adhesion.
authors.affiliation: Department of Biology, Tanabe Research Laboratories, San Diego, California 92121, USA.
authors.forename: R
authors.initials: R
authors.lastname: Tsuruta
authors.forename: R R
authors.initials: RR
authors.lastname: Cobb
authors.forename: M
authors.initials: M
authors.lastname: Mastrangelo
authors.forename: E
authors.initials: E
authors.lastname: Lazarides
authors.forename: P M
authors.initials: PM
authors.lastname: Cardarelli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D004357:Drug Synergism; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D017997:Leukotriene C4 / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D013268:Stimulation, Chemical; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000276:immunology / Q000494:pharmacology*
chemical_list: D007141:Immunoglobulin Fc Fragments; D007476:Ionophores; D010456:Peptides, Cyclic; D010972:Platelet Activating Factor; D011993:Recombinant Fusion Proteins; D019010:Vascular Cell Adhesion Molecule-1; D017997:Leukotriene C4; D000001:Calcimycin