Journal of Leukocyte Biology BioLegend: Treg, Th17, Stem Cell
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Originally published online as doi:10.1189/jlb.0707441 on January 15, 2008

Published online before print January 15, 2008
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(Journal of Leukocyte Biology. 2008;83:1038-1048.)
© 2008 by Society for Leukocyte Biology

Selective blockade of lymphopoiesis induced by kalanchosine dimalate: inhibition of IL-7-dependent proliferation

Luciana S. de Paiva*,1, Alberto Nobrega*,1,2, Giany O. De Melo{dagger}, Elize A. Hayashi*, Vinicius Carvalho{ddagger}, Patricia M. Rodrigues e Silva{ddagger}, Maria Bellio*, Gerlinde P. Teixeira§, Vivian Rumjanek||, Sonia S. Costa{dagger} and Vera Lúcia G. Koatz||

* Departamento de Imunologia, Instituto de Microbiologia,
{dagger} Núcleo de Pesquisas de Produtos Naturais,
|| Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Brazil;
{ddagger} Departamento de Fisiologia e Farmacodinâmica, IOC, FIOCRUZ, Rio de Janeiro, Brazil; and
§ Departamento de Imunobiologia, Instituto de Biologia, Universidade Federal Fluminense, Rio de Janeiro, Brazil

2 Correspondence: Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, Bl.I, sala I2-051, Cidade Universitária, CEP:21941-902, Rio de Janeiro, Brazil. E-mail: afnobrega{at}gmail.com

ABSTRACT

Lymphopoiesis and myelopoiesis continuously generate mature cells from hematopoietic cell progenitors during the lifetime of the organism. The identification of new endogenous or exogenous substances that can act specifically on the differentiation of distinct cell lineages is of relevance and has potential therapeutical use. Kalanchoe brasiliensis (Kb) is a medicinal plant from the Crassulaceae family, used in folk medicine to treat inflammatory and infectious diseases. Here, we show that short-term treatment of naïve mice with Kb led to a strong and selective inhibition of lymphopoiesis, affecting B and T cell lineages without reduction of the myeloid lineage development. Similar effects were observed after treatment with the highly purified compound kalanchosine dimalate (KMC), obtained from Kb. Numbers of mature lymphocytes in secondary lymphoid organs were preserved in Kb(KMC)-treated mice. The effect of Kb(KMC) was not a result of secondary augmentation of plasma levels of endogenous corticoids; neither involves TNF-{alpha}, type-I IFN, or TLR2/TLR4 ligands, which have all been described as selective inhibitors of lymphopoiesis. Flow cytometry analysis of the phenotypes of T and B cell precursors indicate a blockade of maturation on IL-7-dependent, proliferative stages. In vitro, Kb(KMC) inhibited the IL-7-dependent proliferation of pre-B cells and does not induce massive apoptosis of B and T cell precursors. These results suggest that Kb(KMC) is selectively blocking lymphopoiesis through a mechanism that does not involve the previously characterized substances, possibly acting on the IL-7 signaling pathway, opening new perspectives for a potential therapeutic use of Kb-derived drugs.

Key Words: Kalanchoe brasiliensis • corticosteroids • TLR • IFN • TNF






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