Fibrinogen γ-Chain Peptide–Coated Adenosine 5′ Diphosphate–Encapsulated Liposomes Rescue Mice From Lethal Blast Lung Injury via Adenosine Signaling

Kohsuke Hagisawa, Manabu Kinoshita, Hiroki Miyawaki, Shunichi Sato, Hiromi Miyazaki, Shinji Takeoka, Hidenori Suzuki, Keiichi Iwaya, Shuhji Seki, Satoshi Shono, Daizoh Saitoh, Yasuhiro Nishida, Makoto Handa

Research output: Contribution to journalArticle

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Abstract

OBJECTIVES:: Fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes can accumulate via dodecapeptide HHLGGAKQAGDV interactions at bleeding sites where they release adenosine 5′-diphosphate that is rapidly metabolized to adenosine, which has tissue-protective effects. We investigated the efficacy of fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes to treat blast lung injury, with a focus on adenosine signaling. DESIGN:: Controlled animal study. SETTING:: University research laboratory. SUBJECTS:: Adult male C57BL/6 mice. INTERVENTIONS:: Mice were pretreated with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes, dodecapeptide HHLGGAKQAGDV-(phosphate-buffered saline)-liposomes, adenosine 5′ diphosphateliposomes, or phosphate-buffered saline-liposomes. Five minutes after treatment the mice received a single laser-induced shock wave (1.8 J/cm) that caused lethal blast lung injury, and their survival times and lung injuries were then assessed. We also evaluated the therapeutic effect of posttreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes or H12-(phosphate-buffered saline)-liposomes 1 minute after laser-induced shock wave exposure. To examine the effect of adenosine signaling, adenosine A2A receptor (ZM241385) or adenosine A2B receptor (PSB 1115) antagonists were administered to the mice 1 hour before the pretreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes that was followed by laser-induced shock wave exposure. MEASUREMENTS AND MAIN RESULTS:: Pre- and posttreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes significantly increased mouse survival [fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes: 58% survival vs H12-(phosphate-buffered saline)-liposomes: 8%; p <0.05 (posttreatment)] and mitigated pulmonary tissue damage/hemorrhage and neutrophil accumulation after laser-induced shock wave exposure. fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes accumulated at pulmonary vessel injury sites after laser-induced shock wave exposure with both pre- and posttreatment. Furthermore, pretreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes reduced albumin and macrophage inflammatory protein-2 levels in bronchoalveolar lavage fluid. Although fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes pretreatment did not affect blood coagulation activity in the injured mice, its beneficial effect on blast lung injury was significantly abrogated by A2A or A2B adenosine receptor antagonists (A2A antagonist: 17% survival; A2B antagonist: 33% vs dimethyl sulfoxide control: 80%; p <0.05, respectively). CONCLUSIONS:: Fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes may be effective against blast lung injury by promoting tissue-protective adenosine signaling and could represent a novel controlled-release drug delivery system.

Original languageEnglish
JournalCritical Care Medicine
DOIs
Publication statusAccepted/In press - 2016 Apr 6

Fingerprint

Blast Injuries
Lung Injury
Liposomes
Adenosine
Fibrinogen
Lasers
Adenosine A2 Receptor Antagonists
Phosphates
Adenosine A2B Receptors
Chemokine CXCL2
Adenosine A2A Receptors
Hemorrhage
Adenine Nucleotides
Bronchoalveolar Lavage Fluid

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Fibrinogen γ-Chain Peptide–Coated Adenosine 5′ Diphosphate–Encapsulated Liposomes Rescue Mice From Lethal Blast Lung Injury via Adenosine Signaling. / Hagisawa, Kohsuke; Kinoshita, Manabu; Miyawaki, Hiroki; Sato, Shunichi; Miyazaki, Hiromi; Takeoka, Shinji; Suzuki, Hidenori; Iwaya, Keiichi; Seki, Shuhji; Shono, Satoshi; Saitoh, Daizoh; Nishida, Yasuhiro; Handa, Makoto.

In: Critical Care Medicine, 06.04.2016.

Research output: Contribution to journalArticle

Hagisawa, K, Kinoshita, M, Miyawaki, H, Sato, S, Miyazaki, H, Takeoka, S, Suzuki, H, Iwaya, K, Seki, S, Shono, S, Saitoh, D, Nishida, Y & Handa, M 2016, 'Fibrinogen γ-Chain Peptide–Coated Adenosine 5′ Diphosphate–Encapsulated Liposomes Rescue Mice From Lethal Blast Lung Injury via Adenosine Signaling', Critical Care Medicine. https://doi.org/10.1097/CCM.0000000000001707
Hagisawa, Kohsuke ; Kinoshita, Manabu ; Miyawaki, Hiroki ; Sato, Shunichi ; Miyazaki, Hiromi ; Takeoka, Shinji ; Suzuki, Hidenori ; Iwaya, Keiichi ; Seki, Shuhji ; Shono, Satoshi ; Saitoh, Daizoh ; Nishida, Yasuhiro ; Handa, Makoto. / Fibrinogen γ-Chain Peptide–Coated Adenosine 5′ Diphosphate–Encapsulated Liposomes Rescue Mice From Lethal Blast Lung Injury via Adenosine Signaling. In: Critical Care Medicine. 2016.
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title = "Fibrinogen γ-Chain Peptide–Coated Adenosine 5′ Diphosphate–Encapsulated Liposomes Rescue Mice From Lethal Blast Lung Injury via Adenosine Signaling",
abstract = "OBJECTIVES:: Fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes can accumulate via dodecapeptide HHLGGAKQAGDV interactions at bleeding sites where they release adenosine 5′-diphosphate that is rapidly metabolized to adenosine, which has tissue-protective effects. We investigated the efficacy of fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes to treat blast lung injury, with a focus on adenosine signaling. DESIGN:: Controlled animal study. SETTING:: University research laboratory. SUBJECTS:: Adult male C57BL/6 mice. INTERVENTIONS:: Mice were pretreated with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes, dodecapeptide HHLGGAKQAGDV-(phosphate-buffered saline)-liposomes, adenosine 5′ diphosphateliposomes, or phosphate-buffered saline-liposomes. Five minutes after treatment the mice received a single laser-induced shock wave (1.8 J/cm) that caused lethal blast lung injury, and their survival times and lung injuries were then assessed. We also evaluated the therapeutic effect of posttreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes or H12-(phosphate-buffered saline)-liposomes 1 minute after laser-induced shock wave exposure. To examine the effect of adenosine signaling, adenosine A2A receptor (ZM241385) or adenosine A2B receptor (PSB 1115) antagonists were administered to the mice 1 hour before the pretreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes that was followed by laser-induced shock wave exposure. MEASUREMENTS AND MAIN RESULTS:: Pre- and posttreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes significantly increased mouse survival [fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes: 58{\%} survival vs H12-(phosphate-buffered saline)-liposomes: 8{\%}; p <0.05 (posttreatment)] and mitigated pulmonary tissue damage/hemorrhage and neutrophil accumulation after laser-induced shock wave exposure. fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes accumulated at pulmonary vessel injury sites after laser-induced shock wave exposure with both pre- and posttreatment. Furthermore, pretreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes reduced albumin and macrophage inflammatory protein-2 levels in bronchoalveolar lavage fluid. Although fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes pretreatment did not affect blood coagulation activity in the injured mice, its beneficial effect on blast lung injury was significantly abrogated by A2A or A2B adenosine receptor antagonists (A2A antagonist: 17{\%} survival; A2B antagonist: 33{\%} vs dimethyl sulfoxide control: 80{\%}; p <0.05, respectively). CONCLUSIONS:: Fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes may be effective against blast lung injury by promoting tissue-protective adenosine signaling and could represent a novel controlled-release drug delivery system.",
author = "Kohsuke Hagisawa and Manabu Kinoshita and Hiroki Miyawaki and Shunichi Sato and Hiromi Miyazaki and Shinji Takeoka and Hidenori Suzuki and Keiichi Iwaya and Shuhji Seki and Satoshi Shono and Daizoh Saitoh and Yasuhiro Nishida and Makoto Handa",
year = "2016",
month = "4",
day = "6",
doi = "10.1097/CCM.0000000000001707",
language = "English",
journal = "Critical Care Medicine",
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TY - JOUR

T1 - Fibrinogen γ-Chain Peptide–Coated Adenosine 5′ Diphosphate–Encapsulated Liposomes Rescue Mice From Lethal Blast Lung Injury via Adenosine Signaling

AU - Hagisawa, Kohsuke

AU - Kinoshita, Manabu

AU - Miyawaki, Hiroki

AU - Sato, Shunichi

AU - Miyazaki, Hiromi

AU - Takeoka, Shinji

AU - Suzuki, Hidenori

AU - Iwaya, Keiichi

AU - Seki, Shuhji

AU - Shono, Satoshi

AU - Saitoh, Daizoh

AU - Nishida, Yasuhiro

AU - Handa, Makoto

PY - 2016/4/6

Y1 - 2016/4/6

N2 - OBJECTIVES:: Fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes can accumulate via dodecapeptide HHLGGAKQAGDV interactions at bleeding sites where they release adenosine 5′-diphosphate that is rapidly metabolized to adenosine, which has tissue-protective effects. We investigated the efficacy of fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes to treat blast lung injury, with a focus on adenosine signaling. DESIGN:: Controlled animal study. SETTING:: University research laboratory. SUBJECTS:: Adult male C57BL/6 mice. INTERVENTIONS:: Mice were pretreated with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes, dodecapeptide HHLGGAKQAGDV-(phosphate-buffered saline)-liposomes, adenosine 5′ diphosphateliposomes, or phosphate-buffered saline-liposomes. Five minutes after treatment the mice received a single laser-induced shock wave (1.8 J/cm) that caused lethal blast lung injury, and their survival times and lung injuries were then assessed. We also evaluated the therapeutic effect of posttreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes or H12-(phosphate-buffered saline)-liposomes 1 minute after laser-induced shock wave exposure. To examine the effect of adenosine signaling, adenosine A2A receptor (ZM241385) or adenosine A2B receptor (PSB 1115) antagonists were administered to the mice 1 hour before the pretreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes that was followed by laser-induced shock wave exposure. MEASUREMENTS AND MAIN RESULTS:: Pre- and posttreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes significantly increased mouse survival [fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes: 58% survival vs H12-(phosphate-buffered saline)-liposomes: 8%; p <0.05 (posttreatment)] and mitigated pulmonary tissue damage/hemorrhage and neutrophil accumulation after laser-induced shock wave exposure. fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes accumulated at pulmonary vessel injury sites after laser-induced shock wave exposure with both pre- and posttreatment. Furthermore, pretreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes reduced albumin and macrophage inflammatory protein-2 levels in bronchoalveolar lavage fluid. Although fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes pretreatment did not affect blood coagulation activity in the injured mice, its beneficial effect on blast lung injury was significantly abrogated by A2A or A2B adenosine receptor antagonists (A2A antagonist: 17% survival; A2B antagonist: 33% vs dimethyl sulfoxide control: 80%; p <0.05, respectively). CONCLUSIONS:: Fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes may be effective against blast lung injury by promoting tissue-protective adenosine signaling and could represent a novel controlled-release drug delivery system.

AB - OBJECTIVES:: Fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes can accumulate via dodecapeptide HHLGGAKQAGDV interactions at bleeding sites where they release adenosine 5′-diphosphate that is rapidly metabolized to adenosine, which has tissue-protective effects. We investigated the efficacy of fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes to treat blast lung injury, with a focus on adenosine signaling. DESIGN:: Controlled animal study. SETTING:: University research laboratory. SUBJECTS:: Adult male C57BL/6 mice. INTERVENTIONS:: Mice were pretreated with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes, dodecapeptide HHLGGAKQAGDV-(phosphate-buffered saline)-liposomes, adenosine 5′ diphosphateliposomes, or phosphate-buffered saline-liposomes. Five minutes after treatment the mice received a single laser-induced shock wave (1.8 J/cm) that caused lethal blast lung injury, and their survival times and lung injuries were then assessed. We also evaluated the therapeutic effect of posttreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes or H12-(phosphate-buffered saline)-liposomes 1 minute after laser-induced shock wave exposure. To examine the effect of adenosine signaling, adenosine A2A receptor (ZM241385) or adenosine A2B receptor (PSB 1115) antagonists were administered to the mice 1 hour before the pretreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes that was followed by laser-induced shock wave exposure. MEASUREMENTS AND MAIN RESULTS:: Pre- and posttreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes significantly increased mouse survival [fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes: 58% survival vs H12-(phosphate-buffered saline)-liposomes: 8%; p <0.05 (posttreatment)] and mitigated pulmonary tissue damage/hemorrhage and neutrophil accumulation after laser-induced shock wave exposure. fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes accumulated at pulmonary vessel injury sites after laser-induced shock wave exposure with both pre- and posttreatment. Furthermore, pretreatment with fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes reduced albumin and macrophage inflammatory protein-2 levels in bronchoalveolar lavage fluid. Although fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes pretreatment did not affect blood coagulation activity in the injured mice, its beneficial effect on blast lung injury was significantly abrogated by A2A or A2B adenosine receptor antagonists (A2A antagonist: 17% survival; A2B antagonist: 33% vs dimethyl sulfoxide control: 80%; p <0.05, respectively). CONCLUSIONS:: Fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV)-coated adenosine 5′-diphosphate–encapsulated liposomes may be effective against blast lung injury by promoting tissue-protective adenosine signaling and could represent a novel controlled-release drug delivery system.

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