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Inflammation

, Volume 33, Issue 2, pp 119–125 | Cite as

Characterization of ERK Activation in Human Mast Cells Stimulated by Contact with T Cells

  • Adam MorEmail author
  • Irit Shefler
  • Pazit Salamon
  • Yoel Kloog
  • Yoseph A. Mekori
Article

Abstract

Close physical proximity between mast cells and T cells has been demonstrated in several human conditions. We have identified and characterized a novel mast cell activation pathway initiated by contact with T cells, and showed that this pathway is associated with cytokine release. It has been shown recently that Ras is activated in this pathway. Thus, in the present study we further explore the downstream events associated with Ras activation and cytokine release in human mast cells stimulated by contact with T cells. ERK activation in human mast cells stimulated by either contact with T cells or by crosslinking the FC epsilon receptor was studied. Photobleaching experiments were used to study ERK localization. Enzyme linked immunosorbent assay was used to study the cytokine release by human mast cells. We show that stimulation of human mast cells by contact with activated T cells results is sustained ERK activation. Furthermore, sustained ERK activation in these cells is associated with increased dwell time at the nucleus and with IL-8 release. Interestingly, when mast cells were stimulated by crosslinking the FC epsilon receptor I, ERK activation was transient. ERK activation was associated with a shorter dwell time at the nucleus and with TNF-α release. Thus, retaining ERK in the nucleus might be a mechanism utilized by human mast cells to generate different cytokines from a single signaling cascade.

KEY WORDS

mast cells T cells ERK IL-8 

ABBREVIATION

AKT

protein kinase B

ERK

extracellular signal regulated kinase

FCεRI

FC epsilon receptor I

FRAP

fluorescence recovery after photobleaching

GFP

green florescent protein

IL

interleukin

MAPK

mitogen activated protein kinases

MC

mast cells

Ras

Harvey rat sarcoma viral oncogene

TNF

tumor necrosis factor

Notes

ACKNOWLEDGMENTS

This research was supported by the Morasha program of the Israel Science Foundation (Grant No. 1822/07). Adam Mor has received grant support from the Israel Science Foundation. Yoseph Mekori has received grant support from Israel Science Foundation and is the incumbent of the Reiss Chair in Dermatology, Tel Aviv University. We thank Faye Schreiber for editorial assistance.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Adam Mor
    • 1
    • 2
    • 3
    • 4
    Email author
  • Irit Shefler
    • 1
    • 2
  • Pazit Salamon
    • 1
    • 2
  • Yoel Kloog
    • 3
  • Yoseph A. Mekori
    • 1
    • 2
  1. 1.The Laboratory of Allergy and Clinical ImmunologyMeir Medical CenterKfar SabaIsrael
  2. 2.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Department of Neurobiology, The George Weise Faculty of Life SciencesTel Aviv UniversityTel AvivIsrael
  4. 4.Department of MedicineNew York University School of MedicineNew YorkUSA

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