title: Combined effect of IL-17 and blockade of nitric oxide biosynthesis on haematopoiesis in mice.
abstract: OBJECTIVE
  The study was undertaken to extend our investigation concerning both the in vivo activity of interleukin (IL)-17 and the specific role of nitric oxide (NO) in IL-17-induced effects in the process of haematopoiesis.
  
  
  METHODS
  CBA mice were simultaneously treated with IL-17 and/or nitric oxide synthase (NOS) inhibitor, l-NAME, for 5 days and changes within various haematopoietic cell lineages in bone marrow, spleen and peripheral blood were analysed.
  
  
  RESULTS
  Findings showed that administration of both IL-17 and l-NAME stimulated increase in net haematopoiesis in normal mice. IL-17-enhanced myelopoiesis was characterized by stimulation of both femoral and splenic haematopoietic progenitor cells and morphologically recognizable granulocytes. Additionally, IL-17 induced alterations in the frequency of erythroid progenitor cells in both bone marrow and spleen, accompanied with their mobilization to the peripheral blood. As a consequence of these changes in the erythroid cell compartments, significant reticulocytosis was observed, which evidenced that in IL-17-treated mice effective erythropoiesis occurred. Exposure of mice to NOS inhibitor also increased the number of both granulocyte-macrophage and erythroid progenitors in bone marrow and spleens, and these alterations were followed by the mobilization of erythroid progenitors and elevated content of reticulocytes in peripheral blood. The specific role of NO in IL-17-induced haematopoiesis was demonstrated only in the IL-17-reducing effect on bone marrow late stage erythroid progenitors, CFU-E.
  
  
  CONCLUSIONS
  The results demonstrated the involvement of both IL-17 and NO in the regulation of haematopoietic cell activity in various haematopoietic compartments. They further suggest that IL-17 effects are differentially mediated depending on the haematopoietic microenvironments.
authors.affiliation: Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: A
authors.initials: A
authors.lastname: Krstić
authors.forename: J F
authors.initials: JF
authors.lastname: Santibanez
authors.forename: I
authors.initials: I
authors.lastname: Okić
authors.forename: S
authors.initials: S
authors.lastname: Mojsilović
authors.forename: J
authors.initials: J
authors.lastname: Kocić
authors.forename: G
authors.initials: G
authors.lastname: Jovcić
authors.forename: P
authors.initials: P
authors.lastname: Milenković
authors.forename: D
authors.initials: D
authors.lastname: Bugarski
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D020381:Interleukin-17 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013154:Spleen / Q000166:cytology / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D020381:Interleukin-17; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester