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https://hdl.handle.net/2440/73092
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Type: | Journal article |
Title: | Rapid histamine-induced neutrophil recruitment is sphingosine kinase-1 dependent |
Author: | Sun, W. Abeynaike, L. Escarbe, S. Smith, C. Pitson, S. Hickey, M. Bonder, C. |
Citation: | American Journal of Pathology, 2012; 180(4):1740-1750 |
Publisher: | Amer Soc Investigative Pathology Inc |
Issue Date: | 2012 |
ISSN: | 0002-9440 1525-2191 |
Statement of Responsibility: | Wai Y. Sun, Latasha D. Abeynaike, Samantha Escarbe, Charles D. Smith, Stuart M. Pitson, Michael J. Hickey, Claudine S. Bonder |
Abstract: | Leukocyte recruitment to sites of inflammation is critical for the development of acute allergic responses. Rapid P-selectin up-regulation by endothelial cells is a key promoter of leukocyte infiltration in response to mediators such as histamine. However, the mechanisms underpinning this process are still incompletely understood. We examined the role of the sphingosine kinase/sphingosine-1-phosphate (SK/S1P) pathway and showed that in human umbilical vein endothelial cells, histamine rapidly activates SK in an extracellular signal-regulated kinase (ERK) 1/2-dependent manner, concurrent with the induction of P-selectin expression. Histamine activated both SK-1 and SK-2 isoforms; inhibition of SK-1, but not SK-2, attenuated histamine-induced P-selectin up-regulation and neutrophil rolling in vitro. S1P receptor antagonists failed to prevent histamine-induced P-selectin expression, and exogenous S1P did not increase P-selectin expression, suggesting that S1P cell surface receptors are not involved in this process. Finally, the role of both SK-1 and SK-2 in histamine-induced leukocyte rolling in vivo was assessed using pharmacological and genetic methods. Consistent with the in vitro findings, mice pretreated with either sphingosine kinase inhibitor or fingolimod (FTY720) significantly attenuated histamine-induced leukocyte rolling in the cremaster muscle. Similarly, Sphk1(-/-) but not Sphk2(-/-) mice exhibited reduced histamine-induced leukocyte rolling. These findings demonstrate a key role for SK-1 in histamine-induced rapid P-selectin up-regulation and associated leukocyte rolling, and suggest that endothelial SK-1 is an important contributor to allergic inflammation. |
Keywords: | Cells, Cultured Animals Mice, Knockout Humans Mice Sphingosine Propylene Glycols Histamine Phosphotransferases (Alcohol Group Acceptor) P-Selectin Receptors, Lysosphingolipid Immunosuppressive Agents Enzyme Inhibitors Leukocyte Count Leukocyte Rolling MAP Kinase Signaling System Neutrophil Infiltration Up-Regulation Hemodynamics Human Umbilical Vein Endothelial Cells Fingolimod Hydrochloride |
Rights: | Copyright © 2012 American Society for Investigative Pathology. |
DOI: | 10.1016/j.ajpath.2011.12.024 |
Published version: | http://dx.doi.org/10.1016/j.ajpath.2011.12.024 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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