Lymphotoxin-β Receptor Activation by Activated T Cells Induces Cytokine Release from Mouse Bone Marrow-Derived Mast Cells

c-kit ligand (KL) activated mouse bone marrow-derived mast cells (BMMC) for the dose- and time-dependent release of arachidonic acid from cell membrane phospholipids, with generation of leukotriene (LT) C4 in preference to prostaglandin (PG)D2. KL at concentrations of 10 ng/ml elicited half-maximal eicosanoid generation and at concentrations of > 50 ng/ml elicited a maximal generation of approximately 15 ng LTC4 and 1 ng PGD2 per 10(6) cells, with 20% net beta-hexosaminidase release 10 min after stimulation. Of the other cytokines tested, none, either alone or in combination with KL, elicited or modulated the immediate phase of mediator release by BMMC, indicating strict specificity for KL. Activation of BMMC in response to KL was accompanied by transient phosphorylation of cytosolic phospholipase A2 and reversible translocation of 5-lipoxygenase to a cell membrane fraction 2-5 min after stimulation, when the rate of arachidonic acid release and LTC4 production were maximal. BMMC continuously exposed to KL in the presence of IL-10 and IL-1 beta generated LTC4 in marked preference to PGD2 over the first 10 min followed by delayed generation of PGD2 with no LTC4 over several hours. Pharmacologic studies revealed that PGD2 generation in the immediate phase depended on prostaglandin endoperoxide synthase (PGHS)-1 and in the delayed phase on PGHS-2. Thus, KL provided a nonallergic stimulus for biphasic eicosanoid generation by mast cells. The immediate phase is dominated by LTC4 generation with kinetics and postreceptor biosynthetic events similar to those observed after cell activation through the high affinity IgE receptor, whereas the delayed phase of slow and selective PGD2 production is mediated by induction of PGHS-2.

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Human Mast Cells Release Metalloproteinase-9 on Contact with Activated T Cells: Juxtacrine Regulation by TNF-α

The Journal of Immunology ◽

10.4049/jimmunol.167.7.4008 ◽

2001 ◽

Vol 167 (7) ◽

pp. 4008-4016 ◽

Cited By ~ 153

Author(s):

Dana Baram ◽

Gayle G. Vaday ◽

Pazit Salamon ◽

Ilana Drucker ◽

Rami Hershkoviz ◽

...

Keyword(s):

T Cells ◽

Mast Cells ◽

Activated T Cells ◽

Human Mast Cells ◽

Tnf Α ◽

Metalloproteinase 9

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Granzyme D Is a Novel Murine Mast Cell Protease That Is Highly Induced by Multiple Pathways of Mast Cell Activation

Infection and Immunity ◽

10.1128/iai.00290-13 ◽

2013 ◽

Vol 81 (6) ◽

pp. 2085-2094 ◽

Cited By ~ 3

Author(s):

Elin Rönnberg ◽

Gabriela Calounova ◽

Bengt Guss ◽

Anders Lundequist ◽

Gunnar Pejler

Keyword(s):

T Cells ◽

Mast Cell ◽

Mast Cells ◽

Serine Proteases ◽

Cell Activation ◽

Calcium Ionophore ◽

Mast Cell Activation ◽

Activated T Cells ◽

Mast Cell Protease ◽

Murine Mast Cell

ABSTRACTGranzymes are serine proteases known mostly for their role in the induction of apoptosis. Granzymes A and B have been extensively studied, but relatively little is known about granzymes C to G and K to M. T cells, lymphohematopoietic stromal cells, and granulated metrial gland cells express granzyme D, but the function of granzyme D is unknown. Here we show that granzyme D is expressed by murine mast cells and that its level of expression correlates positively with the extent of mast cell maturation. Coculture of mast cells with live, Gram-positive bacteria caused a profound, Toll-like receptor 2 (TLR2)-dependent induction of granzyme D expression. Granzyme D expression was also induced by isolated bacterial cell wall components, including lipopolysaccharide (LPS) and peptidoglycan, and by stem cell factor, IgE receptor cross-linking, and calcium ionophore stimulation. Granzyme D was released into the medium in response to mast cell activation. Granzyme D induction was dependent on protein kinase C and nuclear factor of activated T cells (NFAT). Together, these findings identify granzyme D as a novel murine mast cell protease and implicate granzyme D in settings where mast cells are activated, such as bacterial infection and allergy.

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Control of hemopoiesis by a bone marrow stromal cell clone: lipopolysaccharide- and interleukin-1-inducible production of colony- stimulating factors

Blood ◽

10.1182/blood.v69.2.682.bloodjournal692682 ◽

1987 ◽

Vol 69 (2) ◽

pp. 682-691 ◽

Cited By ~ 1

Author(s):

D Rennick ◽

G Yang ◽

L Gemmell ◽

F Lee

Keyword(s):

Bone Marrow ◽

Stromal Cell ◽

Cell Clone ◽

Interleukin 1 ◽

Mrna Level ◽

Adherent Cell ◽

Mouse Bone Marrow ◽

Activated T Cells ◽

Gm Csf ◽

Cell Layers

A stromal cell line, GY30, was cloned from mouse bone marrow adherent cell layers. In culture, GY30 cells sustain the production of granulocyte-macrophage progenitor cells (GM-CFU) but fail to support the survival of pluripotential stem cells (CFU-S). GY30 cells secrete two growth factor activities distinct from interleukin-3 (IL-3), IL-2, and macrophage colony-stimulating factor (M-CSF) but functionally similar to GM-CSF and G-CSF. The production of both CSFs is increased 70- to 200-fold by treating GY30 cells with lipopolysaccharide or IL-1. RNA blot analysis reveals the presence of GM-CSF and G-CSF transcripts and demonstrates that IL-1 regulates the production of both factors at the mRNA level. Further, these studies show that the GM-CSF secreted by GY30 cells is structurally similar to the GM-CSF produced by activated T cells.

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