title: Leishmania infection impairs beta 1-integrin function and chemokine receptor expression in mononuclear phagocytes.
abstract: Leishmania spp. are intracellular parasites that cause lesions in the skin, mucosa, and viscera. We have previously shown that Leishmania infection reduces mononuclear phagocyte adhesion to inflamed connective tissue. In this study, we examined the role of adhesion molecules and chemokines in this process. Infection rate (r = -0.826, P = 0.003) and parasite burden (r = -0.917, P = 0.028) negatively correlated to mouse phagocyte adhesion. The decrease (58.7 to 75.0% inhibition, P = 0.005) in phagocyte adhesion to connective tissue, induced by Leishmania, occurred as early as 2 h after infection and was maintained for at least 24 h. Interestingly, impairment of cell adhesion was sustained by phagocyte infection, since it was not observed following phagocytosis of killed parasites (cell adhesion varied from 15.2% below to 24.0% above control levels, P > 0.05). In addition, Leishmania infection diminished cell adhesion to fibronectin (54.1 to 96.2%, P < 0.01), collagen (15.7 to 83.7%, P < 0.05), and laminin (59.1 to 82.2%, P < 0.05). The CD11b(hi) subpopulation was highly infected (49.6 to 97.3%). Calcium and Mg(2+) replacement by Mn(2+), a treatment that is known to induce integrins to a high state of affinity for their receptors, reverted the inhibition in adhesion caused by Leishmania. This reversion was completely blocked by anti-VLA4 antibodies. Furthermore, expression of CCR4 and CCR5, two chemokine receptors implicated in cell adhesion, was found to be downregulated 16 h after infection (2.8 to 4.1 times and 1.9 to 2.8 times, respectively). Together, these results suggest that mechanisms regulating integrin function are implicated in the change of macrophage adhesion in leishmaniasis.
authors.affiliation: LPBI, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão no. 121, Candeal, Salvador, BA 40296-710, Brazil.
authors.forename: Nathanael F
authors.initials: NF
authors.lastname: Pinheiro
authors.forename: Micely D R
authors.initials: MD
authors.lastname: Hermida
authors.forename: Mariana P
authors.initials: MP
authors.lastname: Macedo
authors.forename: José
authors.initials: J
authors.lastname: Mengel
authors.forename: Andre
authors.initials: A
authors.lastname: Bafica
authors.forename: Washington L C
authors.initials: WL
authors.lastname: dos-Santos
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D019012:Integrin beta1 / Q000502:physiology; D007892:Leishmania braziliensis / Q000472:pathogenicity / Q000502:physiology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019012:Integrin beta1; D019707:Receptors, Chemokine