Inhibition of neutrophil elastase attenuates gut mucosal injury evoked by acute alveolar hypoxia in rabbits

Norihito Nakamura, Hiroshi Morisaki, Takeshi Suzuki, Satoshi Yajima, Nobuyuki Katori, Yoshifumi Kotake, Yosuke Funakoshi, Kazuhito Kawabata, Shingo Yamada, Akitoshi Ishizaka, Junzo Takeda

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The aim of the present study was to examine whether neutrophil and its elastase activity played consequential roles in the progression of gut barrier dysfunction during acute alveolar hypoxia by using a specific neutrophil elastase inhibitor, sivelestat. With our institutional approval, 20 male rabbits (weight, 2.0-2.5 kg) were randomly allocated into two groups: control (n = 11) or sivelestat group (n = 9; bolus, 10 mg/kg, followed by 10 mg/kg per hour). At 4 h of alveolar hypoxia exposure (fraction of inspired oxygen, 0.10) under mechanical ventilation, the white blood cell counts and their function to produce oxygen radicals were measured. Intestinal permeability and myeloperoxidase activity were also assessed concurrently with the examination of histological changes of gut mucosa. The examination of sham animals (n = 4) exposed to normoxia was performed under the same study protocol. The circulating leukocyte counts and the neutrophil chemiluminescence were not different between the groups, whereas the neutrophil elastase activity was significantly increased in the control but not in the sivelestat and sham groups. Permeability, leukocyte accumulation, and myeloperoxidase activity of ileal wall in the control group were significantly elevated, accompanied by apparent destruction of gut mucosa compared with the sivelestat group (P < 0.05). Despite no significant differences in systemic inflammatory responses, the neutrophil elastase activity is a key element in the progression of functional and structural injury of gut mucosa during acute alveolar hypoxia.

Original languageEnglish
Pages (from-to)101-105
Number of pages5
JournalShock
Volume28
Issue number1
DOIs
Publication statusPublished - 2007 Jul

Fingerprint

Leukocyte Elastase
Rabbits
Mucous Membrane
Wounds and Injuries
Leukocyte Count
Peroxidase
Permeability
Secretory Proteinase Inhibitory Proteins
Control Groups
Luminescence
Artificial Respiration
Reactive Oxygen Species
Neutrophils
Leukocytes
Oxygen
Weights and Measures
Hypoxia
sivelestat

Keywords

  • Bacterial translocation
  • High-mobility group box 1
  • Leukocyte
  • Permeability
  • Sivelestat

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

Inhibition of neutrophil elastase attenuates gut mucosal injury evoked by acute alveolar hypoxia in rabbits. / Nakamura, Norihito; Morisaki, Hiroshi; Suzuki, Takeshi; Yajima, Satoshi; Katori, Nobuyuki; Kotake, Yoshifumi; Funakoshi, Yosuke; Kawabata, Kazuhito; Yamada, Shingo; Ishizaka, Akitoshi; Takeda, Junzo.

In: Shock, Vol. 28, No. 1, 07.2007, p. 101-105.

Research output: Contribution to journalArticle

Nakamura, N, Morisaki, H, Suzuki, T, Yajima, S, Katori, N, Kotake, Y, Funakoshi, Y, Kawabata, K, Yamada, S, Ishizaka, A & Takeda, J 2007, 'Inhibition of neutrophil elastase attenuates gut mucosal injury evoked by acute alveolar hypoxia in rabbits', Shock, vol. 28, no. 1, pp. 101-105. https://doi.org/10.1097/SHK.0b013e31802fa1b2
Nakamura, Norihito ; Morisaki, Hiroshi ; Suzuki, Takeshi ; Yajima, Satoshi ; Katori, Nobuyuki ; Kotake, Yoshifumi ; Funakoshi, Yosuke ; Kawabata, Kazuhito ; Yamada, Shingo ; Ishizaka, Akitoshi ; Takeda, Junzo. / Inhibition of neutrophil elastase attenuates gut mucosal injury evoked by acute alveolar hypoxia in rabbits. In: Shock. 2007 ; Vol. 28, No. 1. pp. 101-105.
@article{cd5f930ea8b3418e8e94e11309c69e21,
title = "Inhibition of neutrophil elastase attenuates gut mucosal injury evoked by acute alveolar hypoxia in rabbits",
abstract = "The aim of the present study was to examine whether neutrophil and its elastase activity played consequential roles in the progression of gut barrier dysfunction during acute alveolar hypoxia by using a specific neutrophil elastase inhibitor, sivelestat. With our institutional approval, 20 male rabbits (weight, 2.0-2.5 kg) were randomly allocated into two groups: control (n = 11) or sivelestat group (n = 9; bolus, 10 mg/kg, followed by 10 mg/kg per hour). At 4 h of alveolar hypoxia exposure (fraction of inspired oxygen, 0.10) under mechanical ventilation, the white blood cell counts and their function to produce oxygen radicals were measured. Intestinal permeability and myeloperoxidase activity were also assessed concurrently with the examination of histological changes of gut mucosa. The examination of sham animals (n = 4) exposed to normoxia was performed under the same study protocol. The circulating leukocyte counts and the neutrophil chemiluminescence were not different between the groups, whereas the neutrophil elastase activity was significantly increased in the control but not in the sivelestat and sham groups. Permeability, leukocyte accumulation, and myeloperoxidase activity of ileal wall in the control group were significantly elevated, accompanied by apparent destruction of gut mucosa compared with the sivelestat group (P < 0.05). Despite no significant differences in systemic inflammatory responses, the neutrophil elastase activity is a key element in the progression of functional and structural injury of gut mucosa during acute alveolar hypoxia.",
keywords = "Bacterial translocation, High-mobility group box 1, Leukocyte, Permeability, Sivelestat",
author = "Norihito Nakamura and Hiroshi Morisaki and Takeshi Suzuki and Satoshi Yajima and Nobuyuki Katori and Yoshifumi Kotake and Yosuke Funakoshi and Kazuhito Kawabata and Shingo Yamada and Akitoshi Ishizaka and Junzo Takeda",
year = "2007",
month = "7",
doi = "10.1097/SHK.0b013e31802fa1b2",
language = "English",
volume = "28",
pages = "101--105",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Inhibition of neutrophil elastase attenuates gut mucosal injury evoked by acute alveolar hypoxia in rabbits

AU - Nakamura, Norihito

AU - Morisaki, Hiroshi

AU - Suzuki, Takeshi

AU - Yajima, Satoshi

AU - Katori, Nobuyuki

AU - Kotake, Yoshifumi

AU - Funakoshi, Yosuke

AU - Kawabata, Kazuhito

AU - Yamada, Shingo

AU - Ishizaka, Akitoshi

AU - Takeda, Junzo

PY - 2007/7

Y1 - 2007/7

N2 - The aim of the present study was to examine whether neutrophil and its elastase activity played consequential roles in the progression of gut barrier dysfunction during acute alveolar hypoxia by using a specific neutrophil elastase inhibitor, sivelestat. With our institutional approval, 20 male rabbits (weight, 2.0-2.5 kg) were randomly allocated into two groups: control (n = 11) or sivelestat group (n = 9; bolus, 10 mg/kg, followed by 10 mg/kg per hour). At 4 h of alveolar hypoxia exposure (fraction of inspired oxygen, 0.10) under mechanical ventilation, the white blood cell counts and their function to produce oxygen radicals were measured. Intestinal permeability and myeloperoxidase activity were also assessed concurrently with the examination of histological changes of gut mucosa. The examination of sham animals (n = 4) exposed to normoxia was performed under the same study protocol. The circulating leukocyte counts and the neutrophil chemiluminescence were not different between the groups, whereas the neutrophil elastase activity was significantly increased in the control but not in the sivelestat and sham groups. Permeability, leukocyte accumulation, and myeloperoxidase activity of ileal wall in the control group were significantly elevated, accompanied by apparent destruction of gut mucosa compared with the sivelestat group (P < 0.05). Despite no significant differences in systemic inflammatory responses, the neutrophil elastase activity is a key element in the progression of functional and structural injury of gut mucosa during acute alveolar hypoxia.

AB - The aim of the present study was to examine whether neutrophil and its elastase activity played consequential roles in the progression of gut barrier dysfunction during acute alveolar hypoxia by using a specific neutrophil elastase inhibitor, sivelestat. With our institutional approval, 20 male rabbits (weight, 2.0-2.5 kg) were randomly allocated into two groups: control (n = 11) or sivelestat group (n = 9; bolus, 10 mg/kg, followed by 10 mg/kg per hour). At 4 h of alveolar hypoxia exposure (fraction of inspired oxygen, 0.10) under mechanical ventilation, the white blood cell counts and their function to produce oxygen radicals were measured. Intestinal permeability and myeloperoxidase activity were also assessed concurrently with the examination of histological changes of gut mucosa. The examination of sham animals (n = 4) exposed to normoxia was performed under the same study protocol. The circulating leukocyte counts and the neutrophil chemiluminescence were not different between the groups, whereas the neutrophil elastase activity was significantly increased in the control but not in the sivelestat and sham groups. Permeability, leukocyte accumulation, and myeloperoxidase activity of ileal wall in the control group were significantly elevated, accompanied by apparent destruction of gut mucosa compared with the sivelestat group (P < 0.05). Despite no significant differences in systemic inflammatory responses, the neutrophil elastase activity is a key element in the progression of functional and structural injury of gut mucosa during acute alveolar hypoxia.

KW - Bacterial translocation

KW - High-mobility group box 1

KW - Leukocyte

KW - Permeability

KW - Sivelestat

UR - http://www.scopus.com/inward/record.url?scp=34250757078&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250757078&partnerID=8YFLogxK

U2 - 10.1097/SHK.0b013e31802fa1b2

DO - 10.1097/SHK.0b013e31802fa1b2

M3 - Article

C2 - 17483739

AN - SCOPUS:34250757078

VL - 28

SP - 101

EP - 105

JO - Shock

JF - Shock

SN - 1073-2322

IS - 1

ER -