Increased expression and occupancy of receptors for tumour necrosis factor on blood monocytes from tuberculosis patients.

Blood monocytes from tuberculosis patients release high amounts of tumour necrosis factor-alpha (TNF-α). Because the biological efficiency of TNF-α 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 binding ¹²⁵I-TNF-α. We report a slight but not significant enhancement in specific binding of ¹²⁵I -TNF-α on monocytes of 15 consecutively studied patients compared with 10 controls. Percent cell surface bound and internalized ¹²⁵I -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 ¹²⁵I-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 monocytes than on control monocytes, was directly related to the enhanced capacity or 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 ¹²⁵I-TNF-α binding to monocytes 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. [ABSTRACT FROM AUTHOR]