Cyclophilin A cooperates with MIP-2 to augment neutrophil migration

Shannon J Heine1, Denise Olive1, Ji-Liang Gao2, Philip M Murphy2, Michael I Bukrinsky1, Stephanie L Constant11Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA; 2Laboratory of Molecular Immunology, National Institute of Allergy and In...

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Autores principales:	Heine SJ, Olive D, Gao JL, Murphy PM, Bukrinsky MI, Constant SL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/76927e6e004640928cd6c105747c046a
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spelling	oai:doaj.org-article:76927e6e004640928cd6c105747c046a2021-12-02T03:25:39ZCyclophilin A cooperates with MIP-2 to augment neutrophil migration1178-7031https://doaj.org/article/76927e6e004640928cd6c105747c046a2011-06-01T00:00:00Zhttp://www.dovepress.com/cyclophilin-a-cooperates-with-mip-2-to-augment-neutrophil-migration-a7603https://doaj.org/toc/1178-7031Shannon J Heine1, Denise Olive1, Ji-Liang Gao2, Philip M Murphy2, Michael I Bukrinsky1, Stephanie L Constant11Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA; 2Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USABackground: Chemokines contribute to inflammatory responses by inducing leukocyte migration and extravasation. In addition, chemoattractants other than classical chemokines can also be present. Many chemokines have been demonstrated to cooperate, leading to an augmentation in leukocyte recruitment and providing a potential role for the presence of multiple chemoattractants. Extracellular cyclophilins are a group of alternative chemotactic factors, which can be highly elevated during various inflammatory responses and, as we have previously shown, can contribute significantly to neutrophil recruitment in an animal model of acute lung inflammation. In the current studies we investigated whether the most abundant extracellular cyclophilin, CypA, has the capacity to function in partnership with 2 classical chemokines known to be secreted in the same model, macrophage inflammatory protein (MIP)-2/CXCL2 and keratinocyte chemoattractant (KC)/CXCL1.Methods: Neutrophil migration in response to combinations of CypA and MIP-2 or CypA and KC was measured by in vitro chemotaxis assays. Biochemical responses of neutrophils incubated with the combinations of chemoattractants were determined by changes in chemokine receptor internalization and actin polymerization measured by flow cytometry, and changes in intracellular calcium mobilization measured with a calcium sensitive fluorochrome.Results: A combination of CypA and MIP-2, but not KC, augmented neutrophil migration. Based on the level of augmentation, the cooperation between CypA and MIP-2 appeared to be synergistic. Evidence that CypA and MIP-2 cooperate at the biochemical level was demonstrated by increases in receptor internalization, calcium mobilization, and actin polymerization.Conclusion: These findings provide evidence for the capacity of extracellular cyclophilins to interact with classical chemokines, resulting in greater and more efficient leukocyte recruitment.Keywords: chemokine, chemotaxis, inflammationHeine SJOlive DGao JLMurphy PMBukrinsky MIConstant SLDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2011, Iss default, Pp 93-104 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Heine SJ Olive D Gao JL Murphy PM Bukrinsky MI Constant SL Cyclophilin A cooperates with MIP-2 to augment neutrophil migration
description	Shannon J Heine1, Denise Olive1, Ji-Liang Gao2, Philip M Murphy2, Michael I Bukrinsky1, Stephanie L Constant11Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA; 2Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USABackground: Chemokines contribute to inflammatory responses by inducing leukocyte migration and extravasation. In addition, chemoattractants other than classical chemokines can also be present. Many chemokines have been demonstrated to cooperate, leading to an augmentation in leukocyte recruitment and providing a potential role for the presence of multiple chemoattractants. Extracellular cyclophilins are a group of alternative chemotactic factors, which can be highly elevated during various inflammatory responses and, as we have previously shown, can contribute significantly to neutrophil recruitment in an animal model of acute lung inflammation. In the current studies we investigated whether the most abundant extracellular cyclophilin, CypA, has the capacity to function in partnership with 2 classical chemokines known to be secreted in the same model, macrophage inflammatory protein (MIP)-2/CXCL2 and keratinocyte chemoattractant (KC)/CXCL1.Methods: Neutrophil migration in response to combinations of CypA and MIP-2 or CypA and KC was measured by in vitro chemotaxis assays. Biochemical responses of neutrophils incubated with the combinations of chemoattractants were determined by changes in chemokine receptor internalization and actin polymerization measured by flow cytometry, and changes in intracellular calcium mobilization measured with a calcium sensitive fluorochrome.Results: A combination of CypA and MIP-2, but not KC, augmented neutrophil migration. Based on the level of augmentation, the cooperation between CypA and MIP-2 appeared to be synergistic. Evidence that CypA and MIP-2 cooperate at the biochemical level was demonstrated by increases in receptor internalization, calcium mobilization, and actin polymerization.Conclusion: These findings provide evidence for the capacity of extracellular cyclophilins to interact with classical chemokines, resulting in greater and more efficient leukocyte recruitment.Keywords: chemokine, chemotaxis, inflammation
format	article
author	Heine SJ Olive D Gao JL Murphy PM Bukrinsky MI Constant SL
author_facet	Heine SJ Olive D Gao JL Murphy PM Bukrinsky MI Constant SL
author_sort	Heine SJ
title	Cyclophilin A cooperates with MIP-2 to augment neutrophil migration
title_short	Cyclophilin A cooperates with MIP-2 to augment neutrophil migration
title_full	Cyclophilin A cooperates with MIP-2 to augment neutrophil migration
title_fullStr	Cyclophilin A cooperates with MIP-2 to augment neutrophil migration
title_full_unstemmed	Cyclophilin A cooperates with MIP-2 to augment neutrophil migration
title_sort	cyclophilin a cooperates with mip-2 to augment neutrophil migration
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/76927e6e004640928cd6c105747c046a
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Cyclophilin A cooperates with MIP-2 to augment neutrophil migration

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