Plasma fibronectin concentrations in patients with human immunodeficiency virus infection.

Torre, Donato; Issi, M; Sampietro, Carmen; Fiori, G P; Chelazzi, G; Ferraro, Giorgio

doi:10.1136/jcp.43.7.560

Cited by 13 publications

(11 citation statements)

References 14 publications

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“…As a result of HIV-1-induced inflammation and increased protease expression, fibronectin fragments are detected in the blood of HIV-infected patients [54]–[56]. These fragments are believed to promote the transendothelial migration of HIV-1-infected and non-infected leukocytes, and to promote viral stability and cell-to-cell transmission [48], [56], [57].…”

Section: Discussionmentioning

confidence: 99%

Slit2/Robo4 Signaling Modulates HIV-1 gp120-Induced Lymphatic Hyperpermeability

Zhang

Kuzontkoski

et al. 2012

PLoS Pathog

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Dissemination of HIV in the host involves transit of the virus and virus-infected cells across the lymphatic endothelium. HIV may alter lymphatic endothelial permeability to foster dissemination, but the mechanism is largely unexplored. Using a primary human lymphatic endothelial cell model, we found that HIV-1 envelope protein gp120 induced lymphatic hyperpermeability by disturbing the normal function of Robo4, a novel regulator of endothelial permeability. HIV-1 gp120 induced fibronectin expression and integrin α5β1 phosphorylation, which led to the complexing of these three proteins, and their subsequent interaction with Robo4 through its fibronectin type III repeats. Moreover, pretreatment with an active N-terminus fragment of Slit2, a Robo4 agonist, protected lymphatic endothelial cells from HIV-1 gp120-induced hyperpermeability by inhibiting c-Src kinase activation. Our results indicate that targeting Slit2/Robo4 signaling may protect the integrity of the lymphatic barrier and limit the dissemination of HIV in the host.

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Section: Discussionmentioning

confidence: 99%

Slit2/Robo4 Signaling Modulates HIV-1 gp120-Induced Lymphatic Hyperpermeability

Zhang

Kuzontkoski

et al. 2012

PLoS Pathog

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“…Although in this and previous studies, measurement of 450-kDa plasma FN did not identify subsets of patients with distinctive prognoses (31)(32)(33), recent reports suggest that certain fragments, like the III1-C FN fragment, and FN polymers, as may be found in tissue matrices, can enhance infectivity of HIV-1 for CD4 T cells (34,35). FN fragments and native FN have different biological properties (15)(16)(17)(18)(19)(20).…”

Section: Discussionmentioning

confidence: 59%

Monocyte Activation by Circulating Fibronectin Fragments in HIV-1-Infected Patients

Trial

Rubio

Birdsall

et al. 2004

The Journal of Immunology

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To identify signals that can alter leukocyte function in patients receiving highly active antiretroviral therapy (HAART), we analyzed single blood samples from 74 HIV-1-infected patients and additional blood was collected at 90-day intervals from 51 HIV-1-infected patients over a 516 ± 172 (mean ± SD) day interval. Despite the absence of circulating immune complexes and normalization of phagocytic function, compared with controls, the fraction of patients’ monocytes expressing CD49e and CD62L was decreased and expression of CD11b and CD86 increased. Plasma from 63% of patients but none from normal controls contained 110–120 kDa fibronectin fragments (FNf). Presence of FNf did not reflect poor adherence to therapy. Addition of FNf to normal donor blood in vitro replicated changes in monocyte CD49e, CD62L, CD11b, and CD86 seen in vivo. FNf also induced monocytes to release a serine proteinase, nominally identified as proteinase-3, that hydrolyzed cell surface CD49e. α1-Antitrypsin blocked FNf-induced shedding of CD49e in a dose-dependent manner. Plasma with a normal frequency of CD49e+ monocytes contained antiproteases that partially blocked FNf-induced monocyte CD49e shedding, whereas plasma from patients with a low frequency of CD49e+ monocytes did not block this effect of FNf. Electrophoretic analyses of plasma from the latter group of patients suggested that a significant fraction of their α1-antitrypsin was tied up in high molecular mass complexes. These results suggest that monocyte behavior in HIV-1-infected patients may be influenced by FNf and the ratio of protease and antiproteases in the cells’ microenvironment.

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“…Our previous measurements and those of others have demonstrated that concentrations of native 450-kDa plasma fibronectin are not abnormal in HIV-infected patients [16]. …”

Section: Discussionmentioning

confidence: 79%

Monocyte CD49e and 110–120 kDa fibronectin fragments: HIV prognostic indicators independent of viral load and CD4 T-cell counts

Rossen

Rubio

Porter

et al. 2009

Aids

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Objective To investigate the prognostic impact of chronic inflammation associated with HIV infections. Previously, we had observed that proteases, released in the course of HIV infections, cause 110–120 kDa fibronectin fragments (FNf) to appear in the blood of many patients. In vitro, at concentrations within the range found in patients’ plasma, FNf stimulate monocytes to release proteolytic enzymes that remove CD49e from the cell surface and produce cytokines that suppress proliferation of activated T cells when stimulated by agents that crosslink their antigen receptors. Design A long-term observational study of patients whose plasma FNf and monocyte CD49e had been measured at 90-day intervals for 1.4 ± 0.5 years. Methods Plasma FNf was measured by a quantitative western blot assay and monocyte CD49e expression by flow cytometry. Patients were monitored clinically for up to 5 years after enrollment. Results All-cause mortality was significantly higher in patients who had at least 5 μg/ml FNf in more than 50% of plasma samples and/or persistent depletion of monocyte CD49e. Persistence of FNf and depletion of monocyte CD49e were not associated with changes in viral load or CD4 T-cell counts. Conclusion Persistently reduced expression of blood monocyte CD49e and/or the persistent presence of FNf in plasma are adverse prognostic markers in HIV-infected patients.

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Plasma fibronectin concentrations in patients with human immunodeficiency virus infection.

Cited by 13 publications

References 14 publications

Slit2/Robo4 Signaling Modulates HIV-1 gp120-Induced Lymphatic Hyperpermeability

Slit2/Robo4 Signaling Modulates HIV-1 gp120-Induced Lymphatic Hyperpermeability

Monocyte Activation by Circulating Fibronectin Fragments in HIV-1-Infected Patients

Monocyte CD49e and 110–120 kDa fibronectin fragments: HIV prognostic indicators independent of viral load and CD4 T-cell counts

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