title: Modulation of mast cell proliferative and inflammatory responses by leukotriene d4 and stem cell factor signaling interactions.
abstract: Mast cells (MCs) are important effector cells in asthma and pulmonary inflammation, and their proliferation and maturation is maintained by stem cell factor (SCF) via its receptor, c-Kit. Cysteinyl leukotrienes (cys-LTs) are potent inflammatory mediators that signal through CysLT1 R and CysLT2 R located on the MC surface, and they enhance MC inflammatory responses. However, it is not known if SCF and cys-LTs cross-talk and influence MC hyperplasia and activation in inflammation. Here, we report the concerted effort of the growth factor SCF and the inflammatory mediator LTD4 in MC activation. Stimulation of MCs by LTD4 in the presence of SCF enhances c-Kit-mediated proliferative responses. Similarly, SCF synergistically enhances LTD4 -induced calcium, c-fos expression and phosphorylation, as well as MIP1β generation in MCs. These findings suggest that integration of SCF and LTD4 signals may contribute to MC hyperplasia and hyper-reactivity during airway hyper-response and inflammation.
authors.affiliation: Department of Chemistry, University of Akron, Akron, Ohio.
authors.forename: Nosayba
authors.initials: N
authors.lastname: Al-Azzam
authors.forename: Vinay
authors.initials: V
authors.lastname: Kondeti
authors.forename: Ernest
authors.initials: E
authors.lastname: Duah
authors.forename: Farai
authors.initials: F
authors.lastname: Gombedza
authors.forename: Charles K
authors.initials: CK
authors.lastname: Thodeti
authors.forename: Sailaja
authors.initials: S
authors.lastname: Paruchuri
mesh_terms: D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017998:Leukotriene D4 / Q000008:administration & dosage; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D008415:Mastocytosis / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000378:metabolism*
chemical_list: D018077:Receptors, Leukotriene; D019089:Stem Cell Factor; D017998:Leukotriene D4; C412375:cysteinyl leukotriene receptor 2; D019009:Proto-Oncogene Proteins c-kit; C083169:leukotriene D4 receptor; D002118:Calcium