Expression of leukotriene biosynthesis proteins in fetal and adult hematopoietic cells and its functional effects on hematopoiesis
(English)Manuscript (preprint) (Other academic)
Leukotrienes (LT) are potent pro-inflammatory mediators formed from arachidonic acid (AA) in reactions catalyzed by 5-lipoxygenase and either leukotriene A4 hydrolase or leukotriene C4 synthase. 5-lipoxygenase activating protein (FLAP) is also required. We have previously reported expression of FLAP in the hematopoietic compartment of the fetal liver raising questions regarding the role of leukotrienes in hematopoietic regulation. Here we report evidence from in situ hybridization, immunohistochemistry and qRT-PCR experiments that the complete LT biosynthesis machinery is abundantly expressed in hematopoietic cells of the fetal mouse liver from e11.5 until birth. FACS sorting of hematopoietic cells from e15.5 liver and adult bone marrow into different subpopulations followed by quantitative RT-PCR analysis showed that expression was confined mainly to myeloid cells but also detected in hematopoietic stem and progenitor cells. Analysis of FLAP knockout mice showed that a lack of this gene abolished LT and reduced 5(S)- hydroxyeicosa-6E,8Z,11Z,14Z-tetraenoic acid (HETE) production. Furthermore, decreased relative numbers of B-lymphocytes and increased numbers of T-lymphocytes were observed in peripheral blood and increased numbers of common lymphoid progenitor cells were observed in BM. Taken together these findings suggest that production of LTs can occur in cells of the fetal and adult hematopoietic compartments and that deficiency of the FLAP gene (and leukotrienes) may affect lymphocyte maturation.
Leukotriene, hematopoiesis, adult, fetal liver, bone marrow
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-74784OAI: oai:DiVA.org:liu-74784DiVA: diva2:492908