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-alpha). Because the biological efficiency of TNF-alpha would depend on the expression of TNF-alpha receptors on target cells, we thought to analyse the capacity of blood monocytes from a group of patients with pulmonary tuberculosis to bind 125I-TNF-alpha. We report a slight but not significant enhancement in specific binding of 125I-TNF-alpha on monocytes of 15 consecutively studied patients compared with 10 controls. Per cent cell surface bound and internalized 125I-TNF-alpha was identical in the two groups. To evaluate the receptor occupancy by endogenously generated TNF-alpha, similar experiments were performed after cell exposure to low-pH glycine buffer. Under these conditions, specific binding of 125I-TNF-alpha was significantly higher on tuberculosis monocytes compared with control monocytes. Moreover, the occupancy of TNF-alpha receptors by endogenously generated TNF-alpha that was found to be significantly higher on tuberculosis monocytes than on control monocytes, was directly related to the enhanced capacity of mononuclear cells to generate TNF-alpha 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-alpha binding to monocytes without any significant change in the dissociation constant. Collectively, these results indicate an up-regulation of TNF-alpha generation and binding to blood monocytes in patients with pulmonary tuberculosis. They provide support to the hypothesis that TNF-alpha is of critical importance in the pathogenesis of this infection.
Cadranel
J
J
INSERM Unité 64, Hôpital Tenon, Paris, France.
Philippe
C
C
Philippe
B
B
Milleron
B
B
Fouqueray
B
B
Mayaud
C
C
Baud
L
L
D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis* / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000995:Antitubercular Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha