Vol 27 No 2 December - The Indian Society for Parasitology

92 CSF production induced by L. donovani amastigote components JPD : Vol. 27 (2), 2003
also indicate a high order of functional and molecular ACKNOWLEDGEMENTS
similarity between the LDAA-induced CSFs in the
We are grateful to Dr. C. L. Kaul, Director, for his help
serum and CM as evidenced by the similar proportion
and continued encouragement during the course of this
of G, M, and GM colonies formed under the influence
study. Ms. Priya Singal is grateful to the Council of
of CSFs generated from both these sources, as well as
Scientific and Industrial Research, New Delhi for the
by the selective neutralization of individual CSF.
award of a Senior Research Fellowship (National
These observations also suggest a common induction
Entrance Test). Technical assistance rendered by Mr.
mechanism of CSF production, in vivo and in vitro.
Vijay Misra is greatly acknowledged. NIPER,
Additionally, GM-CSF appeared to be the major
communication No. 249.
activity both in the serum and CM.
REFERENCES
Both IL-1 (Lovhaug et al., 1986) and TNF-α (Munker
Armitage JO. 1998. Emerging applications of recombinant human
et al., 1986) are reported to induce the macrophages to
granulocyte-macrophage colony-stimulating factor. Blood.
produce CSFs. Since peritoneal MØs obtained from L. 92: 4491-508.
donovani-infected. mice do not produce IL-1, in vitro
Bogdan C and Rollinghoff M. 1998. The immune response to
(Reiner, 1987), it may not account for the CSF Leishmania: mechanisms of parasite control and evasion. Int J
induction observed in this study. On the other hand, Parasitol. 28: 121-34.
increased TNF-α levels are reported to occur in the Buchsel PC, Forgey A, Grape FB and Hamann SS. 2002.
CM of L. donovani-infected MØs (Moore and Granulocyte-macrophage colony-stimulating factor: current
Matlashewski, 1994) and in the liver of L. donovani- practice and novel approaches. Clin J Oncol Nurs. 6: 198-205.
infected mice (Tumang et al., 1994). Therefore, to Cheers C, Haigh AM, Kelso A, Metcalf D, Stanley ER and Young
AM. 1988. Production of colony-stimulating factor (CSFs)
exclude the possible role of TNF-α in mediating the
during infection: separate determinations of macrophage-,
LDAA-induced production of CSFs, MØs were co- granulocyte-, granulocyte-macrophage- and multi CSFs.
treated with LDAA and neutralizing concentrations of Infect Immun. 56: 247-51.
anti-mouse TNF-α antibody, and the lack of any effect Cotterell SEJ, Engwerda CR and Kaye PM. 2000a. Enhanced
on the CSF production clearly suggested that the hematopoietic activity accompanies parasite expansion in the
LDAA-induced production of CSFs was not mediated spleen and bone marrow of mice infected with Leishmania
by TNF-α.
donovani. Infect Immun. 68: 1840-8.
Cotterell SEJ, Engwerda CR and Kaye PM. 2000b. Leishmania
The biological role(s) of CSFs in leishmaniasis donovani infection of bone marrow stromal macrophages
remains largely unclear. Various reports have selectively enhances myelopoiesis, by a mechanism involving
indicated that GM-CSF has a host protective role - GM-CSF and TNF-α. Blood. 95: 1642-51.
enhancing the intracellular inactivation of the parasite Doherty TM and Coffman RL. 1993. Leishmania antigens
(Handman and Burgess, 1979; Weiser et al., 1987; presented by GM-CSF-derived macrophages protect
susceptible mice against challenge with Leishmania major. J
Doherty and Coffman, 1993). Nevertheless, the
Immunol. 150:5476-83.
precise role(s) of CSFs in various disease states are yet
Donahue RE, Wang EA, Stone DK, Kamen R, Wong GG, Sehgal
to be defined. Our results demonstrating LDAA-
PK, et al. 1986. Stimulation of hematopoiesis in primates by
induced CSF production may have two potential continuous infusion of recombinant human GM-CSF. Nature.
implications: that the CSFs induced may merely serve 321: 872-5.
to increase the number of phagocytes, which are the Freund M and Kleine HD. 1992. The role of GM-CSF in infection.
host cells for parasite expansion "safe targets", as well Infection. 20: S84-92.
as for increasing the phagocytic uptake of the parasite, Grabstein KH, Urdal DL, Tushinski RJ, Mochizuki DY, Price VL,
and the CSFs produced may augment the Cantrell MA, et al. 1986. Induction of macrophage tumoricidal
leishmanicidal activity of the MØs. Therefore, CSFs activity by granulocyte-macrophage colony-stimulating
may play important role(s) in the pathogenesis of VL, factors. Science 232: 506-8.
and detailed studies along these lines will greatly Handman E and Bullen DVR. 2002. Interaction of Leishmania
increase our understanding of the molecular basis of with the host macrophage. Trends Parasitol. 18: 332-4.
the disease processes in VL.
Handman E and Burgess AW. 1979. Stimulation by granulocyte-