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Fetal hepatic expression of 5-lipoxygenase activating protein is confined to colonizing hematopoietic cells
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0003-3927-4394
University of California.
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2009 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 383, no 3, 336-339 p.Article in journal (Refereed) Published
Abstract [en]

Leukotriene C-4 is a potent inflammatory mediator formed from arachidonic acid and glutathione. 5-Lipoxygenase (540), 5-lipoxygenase activating protein (FLAP) and leukotriene C-4 synthase (LTC4S) participate in its biosynthesis. We report evidence from in situ hybridization experiments that FLAP mRNA is abundantly expressed in fetal mouse liver from e11.5 until delivery. In contrast very little or no FLAP mRNA was detected in adult liver. The fetal expression in liver was not uniform but occurred in patches. Cells from e15.5 livers were fractionated by fluorescence activated cell sorting into hepatocytes and other CD45(-) cells and CD45(+) hematopoietic cells. The latter were further separated into immature (Lin(-)) and mature (Lin(+)) cells and analyzed for FLAP mRNA content by quantitative RT-PCR. FLAP mRNA expression was confined to CD45(+) cells and the mature cells had approximately 4-fold higher FLAP mRNA levels compared to the immature cells.

Place, publisher, year, edition, pages
2009. Vol. 383, no 3, 336-339 p.
Keyword [en]
Embryonic development, Fluorescence-activated cell sorting, In situ hybridization, Leukotrienes, 5-Lipoxygenase activating protein, Liver, Hematopoietic cells
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-18568DOI: 10.1016/j.bbrc.2009.04.007ISI: 000265966800012OAI: oai:DiVA.org:liu-18568DiVA: diva2:220603
Available from: 2009-06-01 Created: 2009-06-01 Last updated: 2017-12-13Bibliographically approved
In thesis
1. The enzymatic machinery of leukotriene biosynthesis: Studies on ontogenic expression, interactions and function
Open this publication in new window or tab >>The enzymatic machinery of leukotriene biosynthesis: Studies on ontogenic expression, interactions and function
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Leukotrienes (LTs) are biologically active arachidonic acid (AA) derivatives generated by the 5-lipoxygenase (5-LO) pathway. They are produced by myeloid cells. 5-LO converts AA to LTA4 in cooperation with 5-LO activating protein (FLAP). LTA4 is converted to LTB4, by LTA4-hydrolase (LTA4H) or to LTC4 by LTC4-synthase (LTC4S). LTs act on cells through plasma membrane bound G-protein coupled receptors found on leukocytes, smooth muscle and endothelial cells. We report here protein-protein interactions of proteins involved in LTC4 synthesis. 5-LO interacts with cytosolic domains of the integral membrane proteins FLAP and LTC4S at the nuclear envelope, in addition LTC4S interacts with FLAP through its hydrophobic membrane spanning regions. We constructed an LTC4S promoter controlled GFP reporter vector, displaying cell specific expression and sensitivity to agents known to affect LTC4S expression. The vector was used to create transgenic mice expressing GFP as a reporter for LTC4S. Ontogenic mouse expression studies revealed that the complete LT biosynthesis machinery was present at e11.5 primarily in the hematopoietic cells colonizing the liver. Although mature myeloid cells were the main contributors, a substantial amount of FLAP message was also detected in hematopoietic stem and progenitor cells, indicating possible functions for FLAP in hematopoietic regulation. Functional analyses using FLAP knockout mice suggested fine-tuning roles for LTs during differentiation, primarily along the B-lymphocyte differentiation path.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 103 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1287
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-74785 (URN)978-91-7519-987-0 (ISBN)
Public defence
2012-03-09, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
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Available from: 2012-02-08 Created: 2012-02-08 Last updated: 2017-07-07Bibliographically approved

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Strid, TobiasKarlsson, CeciliaSöderström, MatsQian, HongSigvardsson, MikaelHammarström, Sven

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Biochemical and Biophysical Research Communications - BBRC
Medical and Health Sciences

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