title: Leukotriene B4, an activation product of mast cells, is a chemoattractant for their progenitors.
abstract: Mast cells are tissue-resident cells with important functions in allergy and inflammation. Pluripotential hematopoietic stem cells in the bone marrow give rise to committed mast cell progenitors that transit via the blood to tissues throughout the body, where they mature. Knowledge is limited about the factors that release mast cell progenitors from the bone marrow or recruit them to remote tissues. Mouse femoral bone marrow cells were cultured with IL-3 for 2 wk and a range of chemotactic agents were tested on the c-kit(+) population. Cells were remarkably refractory and no chemotaxis was induced by any chemokines tested. However, supernatants from activated mature mast cells induced pronounced chemotaxis, with the active principle identified as leukotriene (LT) B(4). Other activation products were inactive. LTB(4) was highly chemotactic for 2-wk-old cells, but not mature cells, correlating with a loss of mRNA for the LTB(4) receptor, BLT1. Immature cells also accumulated in vivo in response to intradermally injected LTB(4). Furthermore, LTB(4) was highly potent in attracting mast cell progenitors from freshly isolated bone marrow cell suspensions. Finally, LTB(4) was a potent chemoattractant for human cord blood-derived immature, but not mature, mast cells. These results suggest an autocrine role for LTB(4) in regulating tissue mast cell numbers.
authors.affiliation: Leukocyte Biology Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, England, UK.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Weller
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Collington
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Brown
authors.forename: Hugh R P
authors.initials: HR
authors.lastname: Miller
authors.forename: Adam
authors.initials: A
authors.lastname: Al-Kashi
authors.forename: Peter
authors.initials: P
authors.lastname: Clark
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Jose
authors.forename: Adele
authors.initials: A
authors.lastname: Hartnell
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Williams
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002630:Chemotactic Factors / Q000302:isolation & purification / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism*; D007975:Leukotriene B4 / Q000378:metabolism* / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002630:Chemotactic Factors; D017931:DNA Primers; D007377:Interleukin-3; C513240:LTB4R protein, human; C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; D007975:Leukotriene B4