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Leishmania infection modulates beta-1 integrin activation and alters the kinetics of monocyte spreading over fibronectin.

Figueira CP, Carvalhal DG, Almeida RA, Hermida Md, Touchard D, Robert P, Pierres A, Bongrand P, dos-Santos WL - Sci Rep (2015)

Bottom Line: Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue.This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody.These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis.

View Article: PubMed Central - PubMed

Affiliation: Fundação Oswaldo Cruz-Bahia, Centro de Pesquisas Gonçalo Moniz, Brazilian Ministry of Health, Salvador, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus

The effect of soluble factors from Leishmania on the adhesion capacity of human monocytes.Human monocytes were cultured in the top chamber of transwell modules either alone (M) or with Leishmania (M + L). The bottom chamber contained medium, Leishmania (L), or macrophages and Leishmania (M + L). After 24 h, the cells in the top chamber were collected and subjected to the adhesion assay on surfaces coated with fibronectin or collagen.
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f4: The effect of soluble factors from Leishmania on the adhesion capacity of human monocytes.Human monocytes were cultured in the top chamber of transwell modules either alone (M) or with Leishmania (M + L). The bottom chamber contained medium, Leishmania (L), or macrophages and Leishmania (M + L). After 24 h, the cells in the top chamber were collected and subjected to the adhesion assay on surfaces coated with fibronectin or collagen.

Mentions: To confirm that infection—and not soluble substances released by the Leishmania or by the infected leukocytes—would interfere with monocyte adherence to connective matrix components, we performed an adhesion assay using monocytes cultured in contact with the parasites or separated from them by a permeable membrane in transwell chambers. Only monocytes that were cultured in contact with Leishmania displayed decreased adherence to fibronectin or to collagen (Fig. 4). The monocytes in contact with the parasite showed a 96.2% decrease in adherence to fibronectin and a 92.5% decrease in adherence to collagen in comparison with the uninfected control monocytes cultured with medium alone. Monocytes cultured in a chamber separate from the one containing the Leishmania showed no change in adherence to the connective matrix components (Fig. 4).


Leishmania infection modulates beta-1 integrin activation and alters the kinetics of monocyte spreading over fibronectin.

Figueira CP, Carvalhal DG, Almeida RA, Hermida Md, Touchard D, Robert P, Pierres A, Bongrand P, dos-Santos WL - Sci Rep (2015)

The effect of soluble factors from Leishmania on the adhesion capacity of human monocytes.Human monocytes were cultured in the top chamber of transwell modules either alone (M) or with Leishmania (M + L). The bottom chamber contained medium, Leishmania (L), or macrophages and Leishmania (M + L). After 24 h, the cells in the top chamber were collected and subjected to the adhesion assay on surfaces coated with fibronectin or collagen.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528201&req=5

f4: The effect of soluble factors from Leishmania on the adhesion capacity of human monocytes.Human monocytes were cultured in the top chamber of transwell modules either alone (M) or with Leishmania (M + L). The bottom chamber contained medium, Leishmania (L), or macrophages and Leishmania (M + L). After 24 h, the cells in the top chamber were collected and subjected to the adhesion assay on surfaces coated with fibronectin or collagen.
Mentions: To confirm that infection—and not soluble substances released by the Leishmania or by the infected leukocytes—would interfere with monocyte adherence to connective matrix components, we performed an adhesion assay using monocytes cultured in contact with the parasites or separated from them by a permeable membrane in transwell chambers. Only monocytes that were cultured in contact with Leishmania displayed decreased adherence to fibronectin or to collagen (Fig. 4). The monocytes in contact with the parasite showed a 96.2% decrease in adherence to fibronectin and a 92.5% decrease in adherence to collagen in comparison with the uninfected control monocytes cultured with medium alone. Monocytes cultured in a chamber separate from the one containing the Leishmania showed no change in adherence to the connective matrix components (Fig. 4).

Bottom Line: Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue.This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody.These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis.

View Article: PubMed Central - PubMed

Affiliation: Fundação Oswaldo Cruz-Bahia, Centro de Pesquisas Gonçalo Moniz, Brazilian Ministry of Health, Salvador, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus