title: Leishmania infection modulates beta-1 integrin activation and alters the kinetics of monocyte spreading over fibronectin.
abstract: Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue. In this work, we studied the early stages of bond formation between VLA4 and fibronectin, measured the kinetics of membrane alignment and the monocyte cytoplasm spreading area over a fibronectin-coated surface, and studied the expression of high affinity integrin epitope in uninfected and Leishmania-infected human monocytes. Our results show that the initial VLA4-mediated interaction of Leishmania-infected monocyte with a fibronectin-coated surface is preserved, however, the later stage, leukocyte spreading over the substrate is abrogated in Leishmania-infected cells. The median of spreading area was 72 [55-89] μm(2) for uninfected and 41 [34-51] μm(2) for Leishmania-infected monocyte. This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody. After the initial contact with the fibronectrin-coated surface, uninfected monocyte quickly spread the cytoplasm at a 15 μm(2) s(-1) ratio whilst Leishmania-infected monocytes only made small contacts at a 5.5 μm(2) s(-1) ratio. The expression of high affinity epitope by VLA4 (from 39 ± 21% to 14 ± 3%); and LFA1 (from 37 ± 32% to 18 ± 16%) molecules was reduced in Leishmania-infected monocytes. These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis.
authors.affiliation: Fundação Oswaldo Cruz-Bahia, Centro de Pesquisas Gonçalo Moniz, Brazilian Ministry of Health, Salvador, Brazil.
authors.forename: Cláudio Pereira
authors.initials: CP
authors.lastname: Figueira
authors.affiliation: 1] Fundação Oswaldo Cruz-Bahia, Centro de Pesquisas Gonçalo Moniz, Brazilian Ministry of Health, Salvador, Brazil [2] Universidade do Estado da Bahia, Salvador, BA, Brazil.
authors.forename: Djalma Gomes Ferrão
authors.initials: DG
authors.lastname: Carvalhal
authors.affiliation: Fundação Oswaldo Cruz-Bahia, Centro de Pesquisas Gonçalo Moniz, Brazilian Ministry of Health, Salvador, Brazil.
authors.forename: Rafaela Andrade
authors.initials: RA
authors.lastname: Almeida
authors.affiliation: Fundação Oswaldo Cruz-Bahia, Centro de Pesquisas Gonçalo Moniz, Brazilian Ministry of Health, Salvador, Brazil.
authors.forename: Micely d' El-Rei
authors.initials: Md
authors.lastname: Hermida
authors.affiliation: Laboratoire Adhésion Cellulaire et Inflammation, Parc Scientifique de Luminy, Aix-Marseille Université, Marseille, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Touchard
authors.affiliation: Laboratoire Adhésion Cellulaire et Inflammation, Parc Scientifique de Luminy, Aix-Marseille Université, Marseille, France.
authors.forename: Phillipe
authors.initials: P
authors.lastname: Robert
authors.affiliation: Laboratoire Adhésion Cellulaire et Inflammation, Parc Scientifique de Luminy, Aix-Marseille Université, Marseille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Pierres
authors.affiliation: Laboratoire Adhésion Cellulaire et Inflammation, Parc Scientifique de Luminy, Aix-Marseille Université, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bongrand
authors.affiliation: Fundação Oswaldo Cruz-Bahia, Centro de Pesquisas Gonçalo Moniz, Brazilian Ministry of Health, Salvador, Brazil.
authors.forename: Washington L C
authors.initials: WL
authors.lastname: dos-Santos
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D007700:Kinetics; D007891:Leishmania / Q000378:metabolism*; D007896:Leishmaniasis / Q000378:metabolism* / Q000469:parasitology*; D007962:Leukocytes / Q000378:metabolism / Q000469:parasitology; D009000:Monocytes / Q000378:metabolism* / Q000469:parasitology*
chemical_list: D005353:Fibronectins; D039041:Integrin alpha4beta1; D019012:Integrin beta1