Thrombomodulin induces anti-inflammatory effects by inhibiting the rolling adhesion of leukocytes in vivo

Nishizawa, Shino; Kikuta, Junichi; Seno, Shigeto; Kajiki, Masahiro; Tsujita, Ryuichi; Mizuno, Hiroki; Sudo, Takao; Ao, Tomoka; Matsuda, Hideo; Ishii, Masaru

doi:https://doi.org/10.1016/j.jphs.2020.01.001

Thrombomodulin induces anti-inflammatory effects by inhibiting the rolling adhesion of leukocytes in vivo

Nishizawa, Shino; Kikuta, Junichi; Seno, Shigeto et al.

Journal of Pharmacological Sciences, 2020, 143(1), 17-22

Number of Access:1,461（2025-08-14 00:30 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93170

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Title	Thrombomodulin induces anti-inflammatory effects by inhibiting the rolling adhesion of leukocytes in vivo
Creator	CreatorName Nishizawa, Shino
	NRID 1000060710069 1000060710069 researchmap permalink jkikuta jkikuta Scopus Author ID 36637603800 36637603800 CreatorName Kikuta, Junichi
	NRID 1000030432462 1000030432462 ORCID 0000-0003-3861-6444 0000-0003-3861-6444 researchmap permalink ssenoo ssenoo Scopus Author ID 57214748425 57214748425 CreatorName Seno, Shigeto
	CreatorName Kajiki, Masahiro
	CreatorName Tsujita, Ryuichi
	NRID 1000090707655 1000090707655 CreatorName Mizuno, Hiroki
	NRID 1000080631184 1000080631184 researchmap permalink kik kik Scopus Author ID 36497716100 36497716100 CreatorName Sudo, Takao
	NRID 1000090880865 1000090880865 researchmap permalink tomoka_ao1203 tomoka_ao1203 CreatorName Ao, Tomoka
	NRID 1000050183950 1000050183950 ORCID 0000-0002-4701-3779 0000-0002-4701-3779 researchmap permalink Hideo_Matsuda Hideo_Matsuda Scopus Author ID 35381793100 35381793100 CreatorName Matsuda, Hideo
	NRID 1000010324758 1000010324758 researchmap permalink read0076684 read0076684 Scopus Author ID 35074093500 35074093500 CreatorName Ishii, Masaru
Subject	Endothelial cell
	Intravital imaging
	Leukocyte
	Rolling adhesion
	Thrombomodulin
Description	Nishizawa S., Kikuta J., Seno S., et al. Thrombomodulin induces anti-inflammatory effects by inhibiting the rolling adhesion of leukocytes in vivo. Journal of Pharmacological Sciences 143, 17 (2020); https://doi.org/10.1016/j.jphs.2020.01.001.
Abstract	Thrombomodulin (TM) is an integral membrane protein expressed on the surface of vascular endothelial cells that suppresses blood coagulation. Recent studies have shown that TM exhibits anti-inflammatory effects by inhibiting leukocyte recruitment. However, the actual modes of action of TM in vivo remain unclear. Here, we describe the pharmacological effects of recombinant human soluble TM (TM alfa) on leukocyte dynamics in living mice using intravital imaging techniques. Under control conditions, neutrophils exhibited three distinct types of adhesion behavior in vessels: 1) “non-adhesion”, in which cells flowed without vessel adhesion; 2) “rolling adhesion”, in which cells transiently interacted with the endothelium; and 3) “tight binding”, in which cells bound strongly to the endothelial cells. Compared to control conditions, local lipopolysaccharide stimulation resulted in an increased frequency of rolling adhesion that was not homogeneously distributed on vessel walls but occurred at specific endothelial sites. Under inflammatory conditions, TM alfa, particularly the D1 domain which is a lectin-like region of TM, significantly decreased the frequency of rolling adhesion, but did not influence the number of tight bindings. This was the first study to demonstrate that TM alfa exerts anti-inflammatory effects by inhibiting rolling adhesion of neutrophils to vascular endothelial cells in living mice.
Publisher	Japanese Pharmacological Society
Source Title	Journal of Pharmacological Sciences
Volume (Issue)	143(1)
Page	17-22
Date of Issued	2020-05-01
Language	English
Handle URL	https://hdl.handle.net/11094/93170
PISSN	13478613
eISSN	13478648
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.jphs.2020.01.001
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Pharmacological Sciences. 2020, 143(1), p. 17-22
DC.title	Thrombomodulin induces anti-inflammatory effects by inhibiting the rolling adhesion of leukocytes in vivo
DC.creator	Nishizawa, Shino
	Kikuta, Junichi
	Seno, Shigeto
	Kajiki, Masahiro
	Tsujita, Ryuichi
	Mizuno, Hiroki
	Sudo, Takao
	Ao, Tomoka
	Matsuda, Hideo
	Ishii, Masaru
DC.publisher	Japanese Pharmacological Society
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020-05-01
DC.identifier	https://doi.org/10.1016/j.jphs.2020.01.001
DC.subject	Endothelial cell
	Intravital imaging
	Leukocyte
	Rolling adhesion
	Thrombomodulin
DC.description	Nishizawa S., Kikuta J., Seno S., et al. Thrombomodulin induces anti-inflammatory effects by inhibiting the rolling adhesion of leukocytes in vivo. Journal of Pharmacological Sciences 143, 17 (2020); https://doi.org/10.1016/j.jphs.2020.01.001.
DCTERMS.abstract	Thrombomodulin (TM) is an integral membrane protein expressed on the surface of vascular endothelial cells that suppresses blood coagulation. Recent studies have shown that TM exhibits anti-inflammatory effects by inhibiting leukocyte recruitment. However, the actual modes of action of TM in vivo remain unclear. Here, we describe the pharmacological effects of recombinant human soluble TM (TM alfa) on leukocyte dynamics in living mice using intravital imaging techniques. Under control conditions, neutrophils exhibited three distinct types of adhesion behavior in vessels: 1) “non-adhesion”, in which cells flowed without vessel adhesion; 2) “rolling adhesion”, in which cells transiently interacted with the endothelium; and 3) “tight binding”, in which cells bound strongly to the endothelial cells. Compared to control conditions, local lipopolysaccharide stimulation resulted in an increased frequency of rolling adhesion that was not homogeneously distributed on vessel walls but occurred at specific endothelial sites. Under inflammatory conditions, TM alfa, particularly the D1 domain which is a lectin-like region of TM, significantly decreased the frequency of rolling adhesion, but did not influence the number of tight bindings. This was the first study to demonstrate that TM alfa exerts anti-inflammatory effects by inhibiting rolling adhesion of neutrophils to vascular endothelial cells in living mice.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	93170
citation_title	Thrombomodulin induces anti-inflammatory effects by inhibiting the rolling adhesion of leukocytes in vivo
citation_author	Nishizawa, Shino
	Kikuta, Junichi
	Seno, Shigeto
	Kajiki, Masahiro
	Tsujita, Ryuichi
	Mizuno, Hiroki
	Sudo, Takao
	Ao, Tomoka
	Matsuda, Hideo
	Ishii, Masaru
citation_publisher	Japanese Pharmacological Society
citation_language	English
citation_date	2020-05-01
citation_journal_title	Journal of Pharmacological Sciences
citation_volume	143
citation_issue	1
citation_firstpage	17
citation_lastpage	22
citation_doi	https://doi.org/10.1016/j.jphs.2020.01.001
citation_public_url	https://hdl.handle.net/11094/93170

Thrombomodulin induces anti-inflammatory effects by inhibiting the rolling adhesion of leukocytes in vivo

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