title: Quantitative assessment of tuftsin receptor expression and second messenger during in vitro differentiation of peripheral blood derived monocytes of leprosy patients.
abstract: 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.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Khare
authors.forename: L K
authors.initials: LK
authors.lastname: Bhutani
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D006801:Humans; D007918:Leprosy / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics*; D015290:Second Messenger Systems; D015398:Signal Transduction; D014405:Tuftsin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011971:Receptors, Immunologic; C029695:tuftsin receptor; D000242:Cyclic AMP; D006152:Cyclic GMP; D014405:Tuftsin; D002118:Calcium