Plasma gelsolin modulates cellular response to sphingosine 1-phosphate

Robert Bucki; Alina Kulakowska; Fitzroy J. Byfield; Malgorzata Zendzian-Piotrowska; Marcin Baranowski; Michal Marzec; Jessamine P. Winer; Nicholas J. Ciccarelli; Jan Gorski; Wieslaw Drozdowski; Robert Bittman; Paul A. Janmey

doi:10.1152/ajpcell.00051.2010

Plasma gelsolin modulates cellular response to sphingosine 1-phosphate

Robert Bucki, Alina Kulakowska, Fitzroy J. Byfield, Malgorzata Zendzian-Piotrowska, Marcin Baranowski, Michal Marzec, Jessamine P. Winer, Nicholas J. Ciccarelli, Jan Gorski, Wieslaw Drozdowski, Robert Bittman, Paul A. Janmey

43 Citations (Scopus)

Abstract

Hypogelsolinemia is observed in patients with different states of acute or chronic inflammation such as sepsis, rheumatoid arthritis, and multiple sclerosis. In animal models of sepsis, repletion of plasma gelsolin reduces septic mortality. However, the functions of extracellular gelsolin and the mechanisms leading to its protective nature are poorly understood. Potential mechanisms involve gelsolin's extracellular actin scavenging function or its ability to bind bioactive lipids or proinflammatory mediators, which would limit inflammatory responses and prevent tissue damage. Here we report that human plasma gelsolin binds to sphingosine 1-phosphate (S1P), a pleiotropic cellular agonist involved in various immune responses, and to its synthetic structural analog FTY720P (Gilenya). The fluorescence intensity of a rhodamine B-labeled phosphatidylinositol 4,5-bisphosphate binding peptide derived from gelsolin and the optical density of recombinant human plasma gelsolin (rhpGSN) were found to decrease after the addition of S1P or FTY720P. Gelsolin's ability to depolymerize F-actin also decreased progressively with increasing addition of S1P. Transient increases in phosphorylation of extracellular signal-regulated kinase in bovine aortic endothelial cells (BAECs) after S1P treatment were inhibited by rhpGSN. The ability of S1P to increase F-actin content and the elastic modulus of primary astrocytes and BAECs was also prevented by rhpGSN. Evaluation of S1P and gelsolin levels in cerebrospinal fluid reveals a low concentration of gelsolin and a high concentration of S1P in samples obtained from patients suffering from lymphatic meningitis. These findings suggest that gelsolin-mediated regulation of S1P bioactivity may be important to maintain immunomodulatory balance at inflammatory sites.

Original language	English
Journal	American Journal of Physiology: Cell Physiology
Volume	299
Issue number	6
Pages (from-to)	C1516-23
ISSN	1522-1563
DOIs	https://doi.org/10.1152/ajpcell.00051.2010
Publication status	Published - Dec 2010
Externally published	Yes

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Bucki, R., Kulakowska, A., Byfield, F. J., Zendzian-Piotrowska, M., Baranowski, M., Marzec, M., Winer, J. P., Ciccarelli, N. J., Gorski, J., Drozdowski, W., Bittman, R., & Janmey, P. A. (2010). Plasma gelsolin modulates cellular response to sphingosine 1-phosphate. American Journal of Physiology: Cell Physiology, 299(6), C1516-23. https://doi.org/10.1152/ajpcell.00051.2010

@article{6d917781c00347f28e5939df003be73e,

title = "Plasma gelsolin modulates cellular response to sphingosine 1-phosphate",

abstract = "Hypogelsolinemia is observed in patients with different states of acute or chronic inflammation such as sepsis, rheumatoid arthritis, and multiple sclerosis. In animal models of sepsis, repletion of plasma gelsolin reduces septic mortality. However, the functions of extracellular gelsolin and the mechanisms leading to its protective nature are poorly understood. Potential mechanisms involve gelsolin's extracellular actin scavenging function or its ability to bind bioactive lipids or proinflammatory mediators, which would limit inflammatory responses and prevent tissue damage. Here we report that human plasma gelsolin binds to sphingosine 1-phosphate (S1P), a pleiotropic cellular agonist involved in various immune responses, and to its synthetic structural analog FTY720P (Gilenya). The fluorescence intensity of a rhodamine B-labeled phosphatidylinositol 4,5-bisphosphate binding peptide derived from gelsolin and the optical density of recombinant human plasma gelsolin (rhpGSN) were found to decrease after the addition of S1P or FTY720P. Gelsolin's ability to depolymerize F-actin also decreased progressively with increasing addition of S1P. Transient increases in phosphorylation of extracellular signal-regulated kinase in bovine aortic endothelial cells (BAECs) after S1P treatment were inhibited by rhpGSN. The ability of S1P to increase F-actin content and the elastic modulus of primary astrocytes and BAECs was also prevented by rhpGSN. Evaluation of S1P and gelsolin levels in cerebrospinal fluid reveals a low concentration of gelsolin and a high concentration of S1P in samples obtained from patients suffering from lymphatic meningitis. These findings suggest that gelsolin-mediated regulation of S1P bioactivity may be important to maintain immunomodulatory balance at inflammatory sites.",

author = "Robert Bucki and Alina Kulakowska and Byfield, {Fitzroy J.} and Malgorzata Zendzian-Piotrowska and Marcin Baranowski and Michal Marzec and Winer, {Jessamine P.} and Ciccarelli, {Nicholas J.} and Jan Gorski and Wieslaw Drozdowski and Robert Bittman and Janmey, {Paul A.}",

note = "M1 - Copyright (C) 2018 U.S. National Library of Medicine. MEDLINE AN 2011005745(Journal; Article; (JOURNAL ARTICLE); (RESEARCH SUPPORT, N.I.H., EXTRAMURAL); (RESEARCH SUPPORT, NON-U.S. GOV'T))",

year = "2010",

month = dec,

doi = "10.1152/ajpcell.00051.2010",

language = "English",

volume = "299",

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T1 - Plasma gelsolin modulates cellular response to sphingosine 1-phosphate

AU - Bucki, Robert

AU - Kulakowska, Alina

AU - Byfield, Fitzroy J.

AU - Zendzian-Piotrowska, Malgorzata

AU - Baranowski, Marcin

AU - Marzec, Michal

AU - Winer, Jessamine P.

AU - Ciccarelli, Nicholas J.

AU - Gorski, Jan

AU - Drozdowski, Wieslaw

AU - Bittman, Robert

AU - Janmey, Paul A.

PY - 2010/12

Y1 - 2010/12

N2 - Hypogelsolinemia is observed in patients with different states of acute or chronic inflammation such as sepsis, rheumatoid arthritis, and multiple sclerosis. In animal models of sepsis, repletion of plasma gelsolin reduces septic mortality. However, the functions of extracellular gelsolin and the mechanisms leading to its protective nature are poorly understood. Potential mechanisms involve gelsolin's extracellular actin scavenging function or its ability to bind bioactive lipids or proinflammatory mediators, which would limit inflammatory responses and prevent tissue damage. Here we report that human plasma gelsolin binds to sphingosine 1-phosphate (S1P), a pleiotropic cellular agonist involved in various immune responses, and to its synthetic structural analog FTY720P (Gilenya). The fluorescence intensity of a rhodamine B-labeled phosphatidylinositol 4,5-bisphosphate binding peptide derived from gelsolin and the optical density of recombinant human plasma gelsolin (rhpGSN) were found to decrease after the addition of S1P or FTY720P. Gelsolin's ability to depolymerize F-actin also decreased progressively with increasing addition of S1P. Transient increases in phosphorylation of extracellular signal-regulated kinase in bovine aortic endothelial cells (BAECs) after S1P treatment were inhibited by rhpGSN. The ability of S1P to increase F-actin content and the elastic modulus of primary astrocytes and BAECs was also prevented by rhpGSN. Evaluation of S1P and gelsolin levels in cerebrospinal fluid reveals a low concentration of gelsolin and a high concentration of S1P in samples obtained from patients suffering from lymphatic meningitis. These findings suggest that gelsolin-mediated regulation of S1P bioactivity may be important to maintain immunomodulatory balance at inflammatory sites.

AB - Hypogelsolinemia is observed in patients with different states of acute or chronic inflammation such as sepsis, rheumatoid arthritis, and multiple sclerosis. In animal models of sepsis, repletion of plasma gelsolin reduces septic mortality. However, the functions of extracellular gelsolin and the mechanisms leading to its protective nature are poorly understood. Potential mechanisms involve gelsolin's extracellular actin scavenging function or its ability to bind bioactive lipids or proinflammatory mediators, which would limit inflammatory responses and prevent tissue damage. Here we report that human plasma gelsolin binds to sphingosine 1-phosphate (S1P), a pleiotropic cellular agonist involved in various immune responses, and to its synthetic structural analog FTY720P (Gilenya). The fluorescence intensity of a rhodamine B-labeled phosphatidylinositol 4,5-bisphosphate binding peptide derived from gelsolin and the optical density of recombinant human plasma gelsolin (rhpGSN) were found to decrease after the addition of S1P or FTY720P. Gelsolin's ability to depolymerize F-actin also decreased progressively with increasing addition of S1P. Transient increases in phosphorylation of extracellular signal-regulated kinase in bovine aortic endothelial cells (BAECs) after S1P treatment were inhibited by rhpGSN. The ability of S1P to increase F-actin content and the elastic modulus of primary astrocytes and BAECs was also prevented by rhpGSN. Evaluation of S1P and gelsolin levels in cerebrospinal fluid reveals a low concentration of gelsolin and a high concentration of S1P in samples obtained from patients suffering from lymphatic meningitis. These findings suggest that gelsolin-mediated regulation of S1P bioactivity may be important to maintain immunomodulatory balance at inflammatory sites.

U2 - 10.1152/ajpcell.00051.2010

DO - 10.1152/ajpcell.00051.2010

M3 - Journal article

SN - 0363-6143

VL - 299

SP - C1516-23

JO - American Journal of Physiology: Cell Physiology

JF - American Journal of Physiology: Cell Physiology

IS - 6

ER -

Plasma gelsolin modulates cellular response to sphingosine 1-phosphate

Abstract

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