Open AccessIncreased expression and occupancy of receptors for tumour necrosis factor on blood monocytes from tuberculosis patients
Author(s) -
CADRANEL J.,
PHILIPPE C.,
PHILIPPE B.,
MILLERON B.,
FOUQUERAY B.,
MAYAUD C.,
BAUD L.
Publication year - 1993
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1993.tb05976.x
Subject(s) - tumor necrosis factor alpha , monocyte , receptor , immunology , alpha (finance) , peripheral blood mononuclear cell , tuberculosis , cytokine , medicine , endocrinology , biology , in vitro , pathology , biochemistry , surgery , construct validity , patient satisfaction
SUMMARY Blood monocytes from tuberculosis patients release high amounts of tumour necrosis factor‐alpha (TNF‐α). Because the biological efficiency of TNF‐ot would depend on the expression of TNF‐α receptors on target cells, we thought to analyse the capacity of blood monocytes from a group of patients with pulmonary tuberculosis to bind 125 I‐TNF‐α. We report a slight but not significant enhancement in specific binding of 125 I‐TNF‐α on monocytes of 15 consecutively studied patients compared with 10 controls. Per cent cell surface bound and internalized 125 I‐TNF‐α was identical in the two groups. To evaluate the receptor occupancy by endogenously generated TNF‐α, similar experiments were performed after cell exposure to low‐pH glycine buffer. Under these conditions, specific binding of 125 I‐TNF‐α was significantly higher on tuberculosis monocytes compared with control monocytes. Moreover, the occupancy of TNF‐α receptors by endogenously generated TNF‐α that was found to be significantly higher on tuberculosis monocyles than on control monocytcs. was directly related to the enhanced capacity of mononuclear cells to generate TNF‐α In vitro , It normalized after 3 months of antituberculous therapy. Scatchard analysis of the binding data revealed that tuberculosis infection caused a significant increase in high affinity 125 I‐TNF‐α binding to monocyles without any significant change in the dissociation constant. Collectively, these results indicate an up‐regulation of TNF‐α generation and binding to blood monocytes in patients with pulmonary tuberculosis. They provide support to the hypothesis that TNF‐α is of critical importance in the pathogenesis of this infection.