A novel prodigiosin-like immunosuppressant from an alkalophilic Micrococcus sp.
A novel red pigment, 2,2'-[3-methoxy-1'amyl-5'-methyl-4-(1-pyrryl)] dipyrryl-methene (MAMPDM), which has properties similar to those of prodigiosins, has been isolated for the first time from a bacterium putatively identified as Micrococcus sp. Our studies showed that MAMPDM inhibited proliferation of both human T as well as B cells and murine T cells, in response to polyclonal mitogens, in a concentration-dependent manner while murine B cell proliferation induced by lipopolysaccharide was inhibited only at high concentration. The effect of MAMPDM on constitutive cell cycling was ascertained using four mouse and human tumour cell lines. At 100 nM, the concentration that inhibited con A induced proliferation of mouse spleen cells, the viability of these cell lines was not affected. At 10-100-fold higher concentration of MAMPDM, however, there was a decrease in cell viability with T cell-derived cell lines being more sensitive. MAMPDM did not block the secretion of IL-2 or expression of CD25 though it inhibited the proliferation of con A stimulated T cells. The higher amount of IL-2 in the supernatant of the con A stimulated T cells, cultured in the presence of the immunomodulator, indicated accumulation of IL-2 due to its reduced utilisation. At inhibitory concentration, MAMPDM induced apoptosis in con A stimulated cells. Thus, MAMPDM may have considerable and selective T cell immunosuppressive potential and appears to act by a mechanism distinct from that of other known immunosuppressors.
Pandey
Ruchi
R
Immunology Section, Cell Biology Division, Bhabha Atomic Research Centre, Modular Laboratories, Trombay, Mumbai 400-085, India.
Chander
Ramesh
R
Sainis
K B
KB
D000475:Alkenes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008837:Micrococcus / Q000737:chemistry*; D011353:Prodigiosin / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000032:analysis
C477858:2,2'-(3-methoxy-1'amyl-5'-methyl-4-(1-pyrryl)) dipyrryl-methene; D000475:Alkenes; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011758:Pyrroles; D015375:Receptors, Interleukin-2; D011353:Prodigiosin