title: Enhanced hematopoietic activity accompanies parasite expansion in the spleen and bone marrow of mice infected with Leishmania donovani.
abstract: In this study, we have analyzed hematopoietic activity in the spleen, bone marrow, and blood of BALB/c and scid mice infected with Leishmania donovani. Our analysis demonstrates that infection induces a rapid but transient mobilization of progenitor cells into the circulation, associated with elevated levels of granulocyte/macrophage colony-stimulating factor (GM-CSF) and MIP-1alpha. From 14 to 28 days postinfection, when parasite expansion begins in the spleen and bone marrow, both the frequency and cell cycle activity of hematopoietic progenitors, particulary CFU-granulocyte, monocyte, are dramatically increased in these organs. This is associated with increased accumulation of mRNA for GM-CSF, M-CSF, and G-CSF, but not interleukin-3. Our data also illustrate that hematopoietic activity, as assessed by changes in the frequency of progenitor cell populations and their levels of cell cycle activity, can be regulated in both a T-cell-independent and T-cell-dependent, as well as in an organ-specific, manner. Collectively, these data add to our knowledge of the long-term changes which occur in organs in which L. donovani is able to persist.
authors.affiliation: Department of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: S E
authors.initials: SE
authors.lastname: Cotterell
authors.forename: C R
authors.initials: CR
authors.lastname: Engwerda
authors.forename: P M
authors.initials: PM
authors.lastname: Kaye
mesh_terms: D000818:Animals; D001769:Blood / Q000469:parasitology; D001853:Bone Marrow / Q000469:parasitology*; D002452:Cell Count; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000096:biosynthesis; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells; D007893:Leishmania donovani / Q000254:growth & development*; D007898:Leishmaniasis, Visceral / Q000503:physiopathology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000469:parasitology*; D013997:Time Factors
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor