cyclic-gmp and Leprosy

Tuftsin, a tetrapeptide (Thr-Lys-Pro-Arg) is known to potentiate the immunogenic activity of antigen-fed macrophages. The present study describes the mechanism of action of tuftsin in leprosy patients throughout the spectrum of the disease in vitro as a function of culture age in terms of (A) involvement of second messengers cAMP, cGMP and [Ca2+]i and (B) number of tuftsin binding sites/and their relative affinities on the monocytes/macrophages. There is apparently no direct involvement of either cAMP or cGMP while comparing the stimulated and unstimulated cultures during in vitro differentiation of monocytes (days 1, 3 and 7) or with the spectrum of the disease. Inhibition of superoxide anion release either by verapamil or with Quin 2 clearly demonstrated the involvement of [Ca2+]i as a second messenger during activation of monocytes/macrophages with tuftsin. Scatchard analysis of radiolabelled tuftsin binding data showed only one type of tuftsin receptor (low affinity) on BL/ LL monocytes/macrophages and normal and BT/TT cultures showed a gradual change in receptor number and affinities (low to high) with the maturation of monocytes to macrophages in contrast to BL/LL groups which displayed significantly less number of receptors. This study elicits a model which depicts that the biological responses/metabolic functions of early monocytes of normal and BT/TT gradually increase with the age of the culture till day 3 and tapers off thereafter in the older (day 7) cultures, whereas the monocytes/macrophages of BL/LL group are metabolically active only on day 1. The present study thereby implies that the clearance of leprosy bacilli from lepromatous leprosy lesions as a consequence of local or systemic immunotherapy (in the present study, the macrophage modulation by tuftsin) depends on the influx of new competent macrophages, rather than the local activation of resident lepromatous macrophages.

Topics: Calcium; Cyclic AMP; Cyclic GMP; Humans; Leprosy; Macrophages; Monocytes; Receptors, Immunologic; Second Messenger Systems; Signal Transduction; Tuftsin

The correlation between the lymphocyte blast transformation test and the basal levels of cyclic nucleotides (cAMP and cGMP) in lymphocytes was studied in 30 patients with lepromatous leprosy and 14 healthy persons. Cells in cultures of whole blood were stimulated with PPD and PHA. As compared to healthy persons, leprosy patients showed inversion of the role of cGMP basal levels in proliferative activity of lymphocytes in a response to PPD. The data obtained give rise to a hypothesis which might explain the low effectiveness of immune stimulators in leprosy.

Topics: Adult; Cyclic AMP; Cyclic GMP; Female; Humans; Leprosy; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Phytohemagglutinins; Tuberculin