Stem Cell Factor Has a Suppressive Activity to IgE-Mediated Chemotaxis of Mast Cells

Sawada, Junko; Shimizu, Shinya; Tamatani, Takuya; Kanegasaki, Shiro; Saito, Hirohisa; Tanaka, Akane; Kambe, Naotomo; Nakahata, Tatsutoshi; Matsuda, Hiroshi

doi:10.4049/jimmunol.174.6.3626

Cited by 29 publications

(23 citation statements)

References 60 publications

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“…The SCF-treated cells also exhibited a dramatic decrease in their ability to migrate to LTB 4 , while their response to SCF was conversely enhanced. A similar observation in MCs was made by Sawada et al (49). They found that preincubation of BMMCs and hCBMCs with SCF for even 1 h completely suppressed IgE-mediated chemotaxis to Ag, while their ability to migrate to nerve growth factor remained essentially unchanged.…”

Section: Discussionsupporting

confidence: 63%

“…It is of interest that IgE-mediated chemotaxis to Ag has been shown to be mediated, in part, by LTB 4 (22). Sawada et al (49) concluded that locally produced SCF may have an inhibitory effect on chemotaxis of MCs, contributing to their accumulation and enhancement of functions at the peripheral site of inflammation. Our observations of decreased LTB 4 -mediated chemotaxis and the effects of SCF on the LTB 4 receptors seem to support this hypothesis and suggest that the progressive decrease observed by Weller et al (23) in BLT1 expression and MC chemotaxis during maturation may have been partly induced by SCF in the culture medium.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Leukotriene B4 Receptors BLT1 and BLT2: Expression and Function in Human and Murine Mast Cells

Lundeen

Sun

Karlsson

et al. 2006

The Journal of Immunology

110

111

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Leukotriene B4 (LTB4) is a potent activator and chemoattractant for leukocytes and is implicated in several inflammatory diseases. The actions of LTB4 are mediated by two cell surface receptors, BLT1, which is predominantly expressed in peripheral blood leukocytes, and BLT2, which is expressed more ubiquitously. Recently, BLT1 expression and LTB4-dependent chemotaxis have been reported in immature mast cells (MCs). We now show the first evidence for BLT2 mRNA expression, in addition to BLT1, in murine bone marrow-derived MCs (mBMMCs) and in a human MC line (HMC-1). Protein expression of BLT1 was confirmed by mAb staining in HMC-1 cells and shown to be predominantly intracellular. Both HMC-1 cells and mBMMCs migrated to LTB4 in a dose-dependent manner in chemotaxis assays. Migration to LTB4 could be inhibited by either a BLT1- or BLT2-selective antagonist. Significant dose-dependent migration of mBMMCs also was observed to 12-(S)-hydroxyeicosotetraenoic acid, a BLT2-selective agonist, demonstrating functional BLT2 activity in these cells. Stimulation of mBMMCs with LTB4 induced transient, dose-dependent, ERK phosphorylation and changes in Akt phosphorylation. Dose-dependent ERK phosphorylation also was observed in response to 12-(S)-hydroxyeicosotetraenoic acid, indicating signaling downstream of BLT2. Pretreatment of mBMMCs with stem cell factor significantly down-regulated expression of BLT1 and BLT2 mRNA and inhibited their migration to LTB4. This study demonstrates expression of functional LTB4 receptors, both BLT1 and BLT2, in murine and human MCs and a regulatory role for stem cell factor in their expression. These receptors may mediate recruitment and accumulation of MCs in response to LTB4 production in areas of inflammation.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Leukotriene B4 Receptors BLT1 and BLT2: Expression and Function in Human and Murine Mast Cells

Lundeen

Sun

Karlsson

et al. 2006

The Journal of Immunology

110

111

View full text Add to dashboard Cite

show abstract

“…We note, however, that the effects of SCF noted here were a consequence of short-term exposure to SCF. Long-term exposure to SCF might downregulate FcRI-mediated chemotaxis (Sawada et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Btk-dependent Rac activation and actin rearrangement following FcεRI aggregation promotes enhanced chemotactic responses of mast cells

Kuehn

Rådinger

Brown

et al. 2010

Journal of Cell Science

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SummaryMast cells infiltrate the sites of inflammation associated with chronic atopic disease and during helminth and bacterial infection. This process requires receptor-mediated cell chemotaxis across a concentration gradient of their chemotactic ligands. In vivo, mast cells are likely to be exposed to several such agents, which can cooperate in a synergistic manner to regulate mast cell homing. Here, we report that chemotaxis of mouse bone-marrow-derived mast cells (BMMCs) in response to the chemoattractants stem-cell factor (SCF) and prostaglandin (PG)E 2 , is substantially enhanced following antigen-dependent ligation of the high-affinity receptor for IgE (FcRI). These responses were associated with enhanced activation of phosphoinositide 3-kinase (PI3K), and downstream activation of the tyrosine protein kinase Btk, with subsequent enhanced phospholipase (PL)C-mediated Ca 2+ mobilization, Rac activation and F-actin rearrangement. Antigen-induced chemotaxis, and the ability of antigen to amplify responses mediated by SCF, adenosine and PGE 2 were suppressed following inhibition of PI3K, and were impaired in BMMCs derived from Btk -/-mice. There were corresponding decreases in the PLC-mediated Ca 2+ signal, Rac activation and F-actin rearrangement, which, as they are essential for BMMC chemotaxis, accounts for the impaired migration of Btk-deficient cells. Taken together, these data demonstrate that, by regulating signaling pathways that control F-actin rearrangement, Btk is crucial for the ability of antigen to amplify mast-cell chemotactic responses.

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“…4D). Sawada et al [25], on the other hand, reported that SCF suppresses chemotactic migration of mast cells towards Ag. Our observation of Ag1SCF-induced F-actin depolymerization may be relevant to these observations.…”

Section: Discussionmentioning

confidence: 99%

The transmembrane adaptor protein NTAL signals to mast cell cytoskeleton via the small GTPase Rho

et al. 2010

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The transmembrane adaptor protein NTAL (non-T-cell activation linker) participates in signalosome assembly in hematopoietic cells, but its exact role in cell physiology remains enigmatic. We report here that BM-derived mast cells from NTAL-deficient mice, responding to Ag alone or in combination with SCF, exhibit reduced spreading on fibronectin, enhanced filamentous actin depolymerization and enhanced migration towards Ag relative to WT cells. No such differences between WT and NTAL À/À BM-derived mast cells were observed when SCF alone was used as activator. We have examined the activities of two small GTPases, Rac and Rho, which are important regulators of actin polymerization. Stimulation with Ag and/or SCF enhanced activity of Rac(1,2,3) in both NTAL À/À and WT cells. In contrast, RhoA activity decreased and this trend was much faster and more extensive in NTAL À/À cells, indicating a positive regulatory role of NTAL in the recovery of RhoA activity. After restoring NTAL into NTAL À/À cells, both spreading and actin responses were rescued. This is the first report of a crucial role of NTAL in signaling, via RhoA, to mast cell cytoskeleton.

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Stem Cell Factor Has a Suppressive Activity to IgE-Mediated Chemotaxis of Mast Cells

Cited by 29 publications

References 60 publications

Leukotriene B4 Receptors BLT1 and BLT2: Expression and Function in Human and Murine Mast Cells

Leukotriene B4 Receptors BLT1 and BLT2: Expression and Function in Human and Murine Mast Cells

Btk-dependent Rac activation and actin rearrangement following FcεRI aggregation promotes enhanced chemotactic responses of mast cells

The transmembrane adaptor protein NTAL signals to mast cell cytoskeleton via the small GTPase Rho

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