Intravenous immunoglobulin-induced neutrophil apoptosis in the lung during murine endotoxemia

Michiko Aoyama-Ishikawa, Ayumi Seishu, Saori Kawakami, Noriaki Maeshige, Makoto Miyoshi, Takahiro Ueda, Makoto Usami, Atsunori Nakao, Joji Kotani

Research output: Contribution to journalArticle

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Abstract

Background: The pathophysiologic features of acute respiratory distress syndrome (ARDS) are attributed to neutrophil accumulation and over-activation. Low blood immunoglobulin G concentrations in septic shock patients are associated with higher risk of developing ARDS. This study showed the effects of intravenous immunoglobulin (IVIg) on neutrophil apoptosis and accumulation in the lung during murine endotoxemia. Methods: Male C57BL/6J mice were injected with saline or 7 mg/kg of lipopolysaccharide (LPS), and 3 h later also were injected with saline, IVIg 300 mg/kg, or IVIg 1000 mg/kg intraperitoneally. At 12 h after LPS injection, mice were sacrificed and peripheral blood and lungs were collected. The lung messenger ribonucleic acid expression (tumor necrosis factor-α [TNF-α], inducible nitric oxide synthase [iNOS], and intercellular adhesion molecule-1 [ICAM-1]) was determined using quantitative realtime reverse transcriptase-polymerase chain reaction. Lungs were immersed in 4% paraformaldehyde and then embedded in paraffin. Tissue slices were prepared and stained with naphthol AS-D chloroacetate esterase to detect neutrophils. The numbers of neutrophils (characterized by the segment number of their nuclei) were counted. Peripheral neutrophil apoptosis was detected by annexin V using flow cytometry and lung neutrophil apoptosis was detected by cleaved caspase-3 using immunohistochemistry. Results: The survival rates of the saline group, LPS group, and IVIg group were all 100%. Apoptosis of peripheral blood neutrophils was inhibited by LPS. Neutrophil accumulation in the lung was decreased by both IVIg 300 mg/kg and 1000 mg/kg. Segmented neutrophils were reduced by IVIg during endotoxemia. However, IVIg 300 mg/kg and 1000 mg/kg had no influence on the lung messenger ribonucleic acid expression of TNF-α, iNOS, or ICAM-1. Cleaved-caspase-3-positive neutrophils were increased in the IVIg 300 mg/kg group during endotoxemia. The 1000 mg/kg IVIG dose reduced the number of segmented neutrophils, but did not induce cleaved-caspase 3-positive neutrophils. Conclusion: A therapeutic IVIg dose can attenuate neutrophil accumulation and regulate neutrophil apoptosis in the lung during endotoxemia. It is possible that the pathways by which IVIG induces neutrophil apoptosis may differ depending on the IVIg concentration.

Original languageEnglish
Pages (from-to)36-42
Number of pages7
JournalSurgical Infections
Volume15
Issue number1
DOIs
Publication statusPublished - Feb 1 2014
Externally publishedYes

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Endotoxemia
Intravenous Immunoglobulins
Neutrophils
Apoptosis
Lung
Lipopolysaccharides
Caspase 3
Adult Respiratory Distress Syndrome
Nitric Oxide Synthase Type II
Intercellular Adhesion Molecule-1
Tumor Necrosis Factor-alpha
Naphthol AS D Esterase
RNA
Annexin A5
Septic Shock
Reverse Transcriptase Polymerase Chain Reaction
Inbred C57BL Mouse
Paraffin

ASJC Scopus subject areas

  • Surgery
  • Infectious Diseases
  • Microbiology (medical)

Cite this

Aoyama-Ishikawa, M., Seishu, A., Kawakami, S., Maeshige, N., Miyoshi, M., Ueda, T., ... Kotani, J. (2014). Intravenous immunoglobulin-induced neutrophil apoptosis in the lung during murine endotoxemia. Surgical Infections, 15(1), 36-42. https://doi.org/10.1089/sur.2012.227

Intravenous immunoglobulin-induced neutrophil apoptosis in the lung during murine endotoxemia. / Aoyama-Ishikawa, Michiko; Seishu, Ayumi; Kawakami, Saori; Maeshige, Noriaki; Miyoshi, Makoto; Ueda, Takahiro; Usami, Makoto; Nakao, Atsunori; Kotani, Joji.

In: Surgical Infections, Vol. 15, No. 1, 01.02.2014, p. 36-42.

Research output: Contribution to journalArticle

Aoyama-Ishikawa, M, Seishu, A, Kawakami, S, Maeshige, N, Miyoshi, M, Ueda, T, Usami, M, Nakao, A & Kotani, J 2014, 'Intravenous immunoglobulin-induced neutrophil apoptosis in the lung during murine endotoxemia', Surgical Infections, vol. 15, no. 1, pp. 36-42. https://doi.org/10.1089/sur.2012.227
Aoyama-Ishikawa M, Seishu A, Kawakami S, Maeshige N, Miyoshi M, Ueda T et al. Intravenous immunoglobulin-induced neutrophil apoptosis in the lung during murine endotoxemia. Surgical Infections. 2014 Feb 1;15(1):36-42. https://doi.org/10.1089/sur.2012.227
Aoyama-Ishikawa, Michiko ; Seishu, Ayumi ; Kawakami, Saori ; Maeshige, Noriaki ; Miyoshi, Makoto ; Ueda, Takahiro ; Usami, Makoto ; Nakao, Atsunori ; Kotani, Joji. / Intravenous immunoglobulin-induced neutrophil apoptosis in the lung during murine endotoxemia. In: Surgical Infections. 2014 ; Vol. 15, No. 1. pp. 36-42.
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abstract = "Background: The pathophysiologic features of acute respiratory distress syndrome (ARDS) are attributed to neutrophil accumulation and over-activation. Low blood immunoglobulin G concentrations in septic shock patients are associated with higher risk of developing ARDS. This study showed the effects of intravenous immunoglobulin (IVIg) on neutrophil apoptosis and accumulation in the lung during murine endotoxemia. Methods: Male C57BL/6J mice were injected with saline or 7 mg/kg of lipopolysaccharide (LPS), and 3 h later also were injected with saline, IVIg 300 mg/kg, or IVIg 1000 mg/kg intraperitoneally. At 12 h after LPS injection, mice were sacrificed and peripheral blood and lungs were collected. The lung messenger ribonucleic acid expression (tumor necrosis factor-α [TNF-α], inducible nitric oxide synthase [iNOS], and intercellular adhesion molecule-1 [ICAM-1]) was determined using quantitative realtime reverse transcriptase-polymerase chain reaction. Lungs were immersed in 4{\%} paraformaldehyde and then embedded in paraffin. Tissue slices were prepared and stained with naphthol AS-D chloroacetate esterase to detect neutrophils. The numbers of neutrophils (characterized by the segment number of their nuclei) were counted. Peripheral neutrophil apoptosis was detected by annexin V using flow cytometry and lung neutrophil apoptosis was detected by cleaved caspase-3 using immunohistochemistry. Results: The survival rates of the saline group, LPS group, and IVIg group were all 100{\%}. Apoptosis of peripheral blood neutrophils was inhibited by LPS. Neutrophil accumulation in the lung was decreased by both IVIg 300 mg/kg and 1000 mg/kg. Segmented neutrophils were reduced by IVIg during endotoxemia. However, IVIg 300 mg/kg and 1000 mg/kg had no influence on the lung messenger ribonucleic acid expression of TNF-α, iNOS, or ICAM-1. Cleaved-caspase-3-positive neutrophils were increased in the IVIg 300 mg/kg group during endotoxemia. The 1000 mg/kg IVIG dose reduced the number of segmented neutrophils, but did not induce cleaved-caspase 3-positive neutrophils. Conclusion: A therapeutic IVIg dose can attenuate neutrophil accumulation and regulate neutrophil apoptosis in the lung during endotoxemia. It is possible that the pathways by which IVIG induces neutrophil apoptosis may differ depending on the IVIg concentration.",
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AU - Maeshige, Noriaki

AU - Miyoshi, Makoto

AU - Ueda, Takahiro

AU - Usami, Makoto

AU - Nakao, Atsunori

AU - Kotani, Joji

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N2 - Background: The pathophysiologic features of acute respiratory distress syndrome (ARDS) are attributed to neutrophil accumulation and over-activation. Low blood immunoglobulin G concentrations in septic shock patients are associated with higher risk of developing ARDS. This study showed the effects of intravenous immunoglobulin (IVIg) on neutrophil apoptosis and accumulation in the lung during murine endotoxemia. Methods: Male C57BL/6J mice were injected with saline or 7 mg/kg of lipopolysaccharide (LPS), and 3 h later also were injected with saline, IVIg 300 mg/kg, or IVIg 1000 mg/kg intraperitoneally. At 12 h after LPS injection, mice were sacrificed and peripheral blood and lungs were collected. The lung messenger ribonucleic acid expression (tumor necrosis factor-α [TNF-α], inducible nitric oxide synthase [iNOS], and intercellular adhesion molecule-1 [ICAM-1]) was determined using quantitative realtime reverse transcriptase-polymerase chain reaction. Lungs were immersed in 4% paraformaldehyde and then embedded in paraffin. Tissue slices were prepared and stained with naphthol AS-D chloroacetate esterase to detect neutrophils. The numbers of neutrophils (characterized by the segment number of their nuclei) were counted. Peripheral neutrophil apoptosis was detected by annexin V using flow cytometry and lung neutrophil apoptosis was detected by cleaved caspase-3 using immunohistochemistry. Results: The survival rates of the saline group, LPS group, and IVIg group were all 100%. Apoptosis of peripheral blood neutrophils was inhibited by LPS. Neutrophil accumulation in the lung was decreased by both IVIg 300 mg/kg and 1000 mg/kg. Segmented neutrophils were reduced by IVIg during endotoxemia. However, IVIg 300 mg/kg and 1000 mg/kg had no influence on the lung messenger ribonucleic acid expression of TNF-α, iNOS, or ICAM-1. Cleaved-caspase-3-positive neutrophils were increased in the IVIg 300 mg/kg group during endotoxemia. The 1000 mg/kg IVIG dose reduced the number of segmented neutrophils, but did not induce cleaved-caspase 3-positive neutrophils. Conclusion: A therapeutic IVIg dose can attenuate neutrophil accumulation and regulate neutrophil apoptosis in the lung during endotoxemia. It is possible that the pathways by which IVIG induces neutrophil apoptosis may differ depending on the IVIg concentration.

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