Cytoskeletal organization and functional changes in monocytes from patients with chronic hepatitis B: Relationship with viral replication

Authors

  • Jesús Prieto,

    Corresponding author
    1. Center for Biomedical Research, Departments of Internal Medicine and Immunology, Clinica Universitaria, School of Medicine, University of Navarra, Pamplona 31080, Spain
    • Clinica Universitaria, Apartado 192, 31080 Pamplona, Spain
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  • Alberto Castilla,

    1. Center for Biomedical Research, Departments of Internal Medicine and Immunology, Clinica Universitaria, School of Medicine, University of Navarra, Pamplona 31080, Spain
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  • María-Luisa Subirá,

    1. Center for Biomedical Research, Departments of Internal Medicine and Immunology, Clinica Universitaria, School of Medicine, University of Navarra, Pamplona 31080, Spain
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  • Manuel Serrano,

    1. Center for Biomedical Research, Departments of Internal Medicine and Immunology, Clinica Universitaria, School of Medicine, University of Navarra, Pamplona 31080, Spain
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  • Susana Morte,

    1. Center for Biomedical Research, Departments of Internal Medicine and Immunology, Clinica Universitaria, School of Medicine, University of Navarra, Pamplona 31080, Spain
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  • María-pilar Civeira

    1. Center for Biomedical Research, Departments of Internal Medicine and Immunology, Clinica Universitaria, School of Medicine, University of Navarra, Pamplona 31080, Spain
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Abstract

Monocytes play an important role in the initiation and regulation of the antiviral immune response. These cells have a dense framework of intermediate filaments composed of vimentin monomers. In 35 patients with chronic hepatitis B, 26 healthy controls, seven patients with acute liver damage and eight patients with inactive HBsAg-negative cirrhosis, we investigated the expression of vimentin filaments, C3b and IgGFc receptors, HLA-DR molecules and the phagocytic activity in monocytes purified from venous blood. In the same subjects, we also studied the display of CD2, CD3 and CD5 on lymphocytes.

In patients with chronic hepatitis B manifesting viral replication (n = 21; Group 1), the expression of vimentin filaments and the other functional monocyte parameters were decreased, whereas in patients in the nonreplicative phase of the disease (n = 14; Group 2) and in control cases with various forms of acute liver damage or inactive HBsAg-negative cirrhosis, they were similar to those found in healthy subjects. In Group 1, there was also a selective defect in the display of CD3 on lymphocytes. The expression of this molecule correlated with the functional state of monocytes. In three patients with chronic hepatitis B that changed from the replicative to the nonreplicative phase of the disease, the expression of vimentin filaments in monocytes and of CD3 on lymphocytes increased to normal levels. On the other hand, the incubation of patients' monocytes with γ-interferon corrected the diminished expression of vimentin filaments and the other decreased functional parameters.

These findings show that in the replicative phase of chronic hepatitis B, there are alterations in the initial steps of activation of antiviral immune response and that γ-IFN is able to correct the monocyte dysfunction present in these patients. Furthermore, it is suggested that the expression of immunoreactive vimentin filaments may be a dynamic indicator of the functional state of monocytes.

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