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Acute lung injury by sepsis and acid aspiration: a key role for cytosolic phospholipase A2

Nature Immunology volume 1, pages 42–46 (2000)Cite this article

Abstract

Adult respiratory distress syndrome (ARDS) is characterized by acute lung injury with a high mortality rate and yet its mechanism is poorly understood. Sepsis syndrome and acid aspiration are the most frequent causes of ARDS, leading to increased lung permeability, enhanced polymorphonuclear neutrophil (PMN) sequestration and respiratory failure. Using a murine model of acute lung injury induced by septic syndrome or acid aspiration, we investigated the role of cytosolic phospholipase A2 (cPLA2) in ARDS. We found that disruption of the gene encoding cPLA2 significantly reduced pulmonary edema, PMN sequestration and deterioration of gas exchange caused by lipopolysaccharide and zymosan administration. Acute lung injury induced by acid aspiration was similarly reduced in mice with a disrupted cpla2 gene. Our observations suggest that cPLA2 is a mediator of acute lung injury induced by sepsis syndrome or acid aspiration. Thus, the inhibition of cPLA2-initiated pathways may provide a therapeutic approach to acute lung injury, for which no pharmaceutical agents are currently effective.

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Figure 1: The time course of response in lung elastance (EL) in LPS/zymosan-treated groups and saline-treated groups (n = 3 for each group).
Figure 2: Role of cpla2 gene in acute lung injury induced by LPS/zymosan treatment.
Figure 3: Photomicrographs of lung tissues.
Figure 4: The time course of response in lung elastance (EL) in HCl- and saline-treated groups.
Figure 5: Role of cPLA2 gene in acid-induced lung injury.
Figure 6: Photomicrograph of lung tissues.

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Acknowledgements

We thank Y. Suzuki, K. Ishihara, K. Izumisawa, R. Mitsuzono, M. Yoshino, C. Jin, M. Hata and M. Ito (The University of Tokyo) for their technical assistance. We are also grateful to F. Takaku (Jichi Medical School), T. Yokomizo, N. Ito, and D. A.Wong (The University of Tokyo) for valuable suggestions. This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan, and grants from the Human Science Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research.

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Authors and Affiliations

  1. Department of Geriatric Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113, Tokyo, Japan

    Takahide Nagase & Yasuyoshi Ouchi

  2. Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113, Tokyo, Japan

    Naonori Uozumi, Satoshi Ishii, Kazuhiko Kume, Takashi Izumi & Takao Shimizu

  3. CREST of Japan Science and Technology Corporation, Japan

    Takao Shimizu

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  1. Takahide Nagase
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Correspondence to Takao Shimizu.

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Nagase, T., Uozumi, N., Ishii, S. et al. Acute lung injury by sepsis and acid aspiration: a key role for cytosolic phospholipase A2. Nat Immunol 1, 42–46 (2000). https://doi.org/10.1038/76897

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