Abstract
Mast cells are key participants in allergic diseases via activation of high-affinity IgE receptors (FcεRI) resulting in release of proinflammatory mediators. The biochemical pathways linking IgE activation to calcium influx and cytoskeletal changes required for intracellular granule release are incompletely understood. We demonstrate, genetically, that Pak1 is required for this process. In a passive cutaneous anaphylaxis experiment, W sh/W sh mast cell-deficient mice locally reconstituted with Pak1 -/- bone marrow-derived mast cells (BMMCs) experienced strikingly decreased allergen-induced vascular permeability compared with controls. Consistent with the in vivo phenotype, Pak1 -/- BMMCs exhibited a reduction in FcεRI-induced degranulation. Further, Pak1 -/- BMMCs demonstrated diminished calcium mobilization and altered depolymerization of cortical filamentous actin (F-actin) in response to FcεRI stimulation. These data implicate Pak1 as an essential molecular target for modulating acute mast cell responses that contribute to allergic diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 2695-2705 |
| Number of pages | 11 |
| Journal | Blood |
| Volume | 113 |
| Issue number | 12 |
| DOIs | |
| State | Published - Mar 19 2009 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
P21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics. / Allen, Jayme D.; Jaffer, Zahara M.; Park, Su Jung; Burgin, Sarah; Hofmann, Clemens; Sells, Mary Ann; Chen, Shi; Derr-Yellin, Ethel; Michels, Elizabeth G.; McDaniel, Andrew; Bessler, Waylan K.; Ingram, David; Atkinson, Simon J.; Travers, Jeffrey; Chernoff, Jonathan; Clapp, D.
In: Blood, Vol. 113, No. 12, 19.03.2009, p. 2695-2705.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - P21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics
AU - Allen, Jayme D.
AU - Jaffer, Zahara M.
AU - Park, Su Jung
AU - Burgin, Sarah
AU - Hofmann, Clemens
AU - Sells, Mary Ann
AU - Chen, Shi
AU - Derr-Yellin, Ethel
AU - Michels, Elizabeth G.
AU - McDaniel, Andrew
AU - Bessler, Waylan K.
AU - Ingram, David
AU - Atkinson, Simon J.
AU - Travers, Jeffrey
AU - Chernoff, Jonathan
AU - Clapp, D.
PY - 2009/3/19
Y1 - 2009/3/19
N2 - Mast cells are key participants in allergic diseases via activation of high-affinity IgE receptors (FcεRI) resulting in release of proinflammatory mediators. The biochemical pathways linking IgE activation to calcium influx and cytoskeletal changes required for intracellular granule release are incompletely understood. We demonstrate, genetically, that Pak1 is required for this process. In a passive cutaneous anaphylaxis experiment, W sh/W sh mast cell-deficient mice locally reconstituted with Pak1 -/- bone marrow-derived mast cells (BMMCs) experienced strikingly decreased allergen-induced vascular permeability compared with controls. Consistent with the in vivo phenotype, Pak1 -/- BMMCs exhibited a reduction in FcεRI-induced degranulation. Further, Pak1 -/- BMMCs demonstrated diminished calcium mobilization and altered depolymerization of cortical filamentous actin (F-actin) in response to FcεRI stimulation. These data implicate Pak1 as an essential molecular target for modulating acute mast cell responses that contribute to allergic diseases.
AB - Mast cells are key participants in allergic diseases via activation of high-affinity IgE receptors (FcεRI) resulting in release of proinflammatory mediators. The biochemical pathways linking IgE activation to calcium influx and cytoskeletal changes required for intracellular granule release are incompletely understood. We demonstrate, genetically, that Pak1 is required for this process. In a passive cutaneous anaphylaxis experiment, W sh/W sh mast cell-deficient mice locally reconstituted with Pak1 -/- bone marrow-derived mast cells (BMMCs) experienced strikingly decreased allergen-induced vascular permeability compared with controls. Consistent with the in vivo phenotype, Pak1 -/- BMMCs exhibited a reduction in FcεRI-induced degranulation. Further, Pak1 -/- BMMCs demonstrated diminished calcium mobilization and altered depolymerization of cortical filamentous actin (F-actin) in response to FcεRI stimulation. These data implicate Pak1 as an essential molecular target for modulating acute mast cell responses that contribute to allergic diseases.
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UR - http://www.scopus.com/inward/citedby.url?scp=63849230362&partnerID=8YFLogxK
U2 - 10.1182/blood-2008-06-160861
DO - 10.1182/blood-2008-06-160861
M3 - Article
C2 - 19124833
AN - SCOPUS:63849230362
VL - 113
SP - 2695
EP - 2705
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -