Rho and Rac, but not ROCK, are required for secretion of human and mouse eosinophil-associated RNases
Corresponding Author
Revital Shamri
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Correspondence
Revital Shamri, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Emails: [email protected], [email protected]
Search for more papers by this authorKristen M. Young
Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Search for more papers by this authorPeter F. Weller
Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Search for more papers by this authorCorresponding Author
Revital Shamri
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Correspondence
Revital Shamri, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Emails: [email protected], [email protected]
Search for more papers by this authorKristen M. Young
Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Search for more papers by this authorPeter F. Weller
Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Search for more papers by this authorSummary
Background
Eosinophil-associated RNases (EARs) are stored preformed in eosinophil cytoplasmic secretory granules and have a key role in eosinophil effector functions in host defence and inflammatory disorders. However, the secretion mechanisms of EARs are poorly understood.
Objective
Our study aimed to understand the involvement of cytoskeleton machinery in EAR secretion.
Methods
Fresh human and mouse eosinophils were stimulated with CCL11, and the secretion of enzymatically active EARs was detected using an RNase activity assay. The involvement of cytoskeletal elements or microtubules was probed using specific inhibitors.
Results
We found that dynamic polymerization of microtubules and cytoskeletal elements, such as Rho and Rac, is required for chemokine-mediated EAR secretion from human and mouse eosinophils. However, inhibition of ROCK (Rho-associated protein kinase) increased EAR secretion in human and mouse eosinophils even in the absence of chemokine stimulation, suggesting ROCK negatively regulates EAR secretion.
Conclusions
Collectively, these data suggest a cytoskeleton-dependent mechanism of EAR secretion from eosinophils, findings that are pertinent to host defence, allergy and other eosinophil-associated diseases.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
Supporting Information
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| cea13292-sup-0001-FigS1.pdfPDF document, 280.9 KB | |
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| cea13292-sup-0003-FigS3.pdfPDF document, 558.1 KB | |
| cea13292-sup-0004-FigS4.pdfPDF document, 339.2 KB | |
| cea13292-sup-0005-MethodS1.docxWord document, 18.9 KB |
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