title: Kinin B1 receptor regulates interactions between neutrophils and endothelial cells by modulating the levels of Mac-1, LFA-1 and intercellular adhesion molecule-1.
abstract: Kinins are pro-inflammatory peptides that mimic the cardinal features of inflammation. We examined the concept that expression levels of endothelial intercellular adhesion molecule-1 (ICAM-1) and neutrophil integrins Mac-1 and LFA-1 are modulated by the kinin B1 receptor (B1R) agonist, Lys-des[Arg(9)]bradykinin (LDBK). Stimulation of endothelial cells with LDBK increased the levels of ICAM-1 mRNA transcripts/protein, and also of E-selectin and platelet endothelial adhesion molecule-1. ICAM-1 levels increased in a magnitude comparable with that produced by TNF-α. This stimulatory effect was reduced when endothelial cells, which had been previously transfected with a B1R small interfering RNA, were stimulated with LDBK, under comparable conditions. Similarly, LDBK produced a significant increase in protein levels of LFA-1 and Mac-1 integrins in human neutrophils, an effect that was reversed by pretreatment of cells with 10 µg/ml cycloheximide or a B1R antagonist. Functional experiments performed with post-confluent monolayers of endothelial cells stimulated with LDBK and neutrophils primed with TNF-α, and vice versa, resulted in enhanced adhesiveness between both cells. Neutralizing Abs to ICAM-1 and Mac-1 reduced the adhesion between them. Our results indicate that kinin B1R is a novel modulator that promotes adhesion of leukocytes to endothelial cells, critically enhancing the movement of neutrophils from the circulation to sites of inflammation.
authors.affiliation: Laboratorio de Patologia Celular, Instituto de Anatomia, Histologia y Patologia, Universidad Austral de Chile, Valdivia, Chile cfiguero@uach.cl.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Figueroa
authors.affiliation: Laboratorio de Patologia Celular, Instituto de Anatomia, Histologia y Patologia, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carola E
authors.initials: CE
authors.lastname: Matus
authors.affiliation: Laboratorio de Patologia Celular, Instituto de Anatomia, Histologia y Patologia, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Pavicic
authors.affiliation: Instituto de Fisiologia, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Jose
authors.initials: J
authors.lastname: Sarmiento
authors.affiliation: Instituto de Farmacologia y Morfofisiologia, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Hidalgo
authors.affiliation: Instituto de Farmacologia y Morfofisiologia, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Burgos
authors.affiliation: Instituto de Fisiologia, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carlos B
authors.initials: CB
authors.lastname: Gonzalez
authors.affiliation: Laboratorio de Patologia Celular, Instituto de Anatomia, Histologia y Patologia, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Kanti D
authors.initials: KD
authors.lastname: Bhoola
authors.affiliation: Laboratorio de Patologia Celular, Instituto de Anatomia, Histologia y Patologia, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ehrenfeld
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D042783:Endothelial Cells / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007609:Kallidin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D034741:RNA, Small Interfering; D043783:Receptor, Bradykinin B1; D018799:Intercellular Adhesion Molecule-1; D007609:Kallidin; C052787:kallidin, des-Arg(10)-; D003513:Cycloheximide
keywords: CD11a/CD18; CD11b/CD18; Kinin B1 receptor; bradykinin; diapedesis; inflammation