1. Induction of type-IIA secretory phospholipase A2 in animal models of acute lung injury
- Author
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Alain Harf, K. Koumanov, Laurent Brochard, C. Wolf, M. Alaoui-El-Azher, Christophe Delclaux, Lhousseine Touqui, H.L. Attalah, Yongzheng Wu, F. Thouron, Physiopathologie et Thérapeutiques Respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10, Défense innée et inflammation, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Réanimation Médicale [CHU Henri Mondor - APHP] (DHU A-TVB), Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine)-CHU Henri Mondor, Service de physiologie, explorations fonctionnelles [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), The authors would like to thank H. Arita (Shionogi Research laboratory, Osaka, Japan) for the generous gift of the rat sPLA2-IIA cDNA., CHU Henri Mondor-Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Wu, Yongzheng, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Henri Mondor [Créteil]-Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine)
- Subjects
Male ,MESH: Lung Compliance / physiology ,Pathology ,endotoxin ,MESH: Pulmonary Edema / physiopathology ,MESH: Rats, Sprague-Dawley ,Pulmonary compliance ,MESH: Phospholipases A / analysis ,Severity of Illness Index ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Rats, Sprague-Dawley ,0302 clinical medicine ,Pulmonary surfactant ,MESH: Pneumonia / complications ,MESH: Animals ,Respiratory system ,MESH: Pulmonary Alveoli / chemistry ,Lung Compliance ,MESH: Phospholipases A2 ,Respiratory Distress Syndrome ,0303 health sciences ,alpha naphthylthiourea ,medicine.diagnostic_test ,biology ,respiratory system ,MESH: Respiratory Distress Syndrome, Adult / physiopathology ,MESH: Group II Phospholipases A2 ,medicine.anatomical_structure ,Pseudomonas aeruginosa ,MESH: Pulmonary Edema / complications ,Pulmonary alveolus ,Bronchoalveolar Lavage Fluid ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,MESH: Rats ,Pulmonary Edema ,Lung injury ,Group II Phospholipases A2 ,compliance ,Phospholipases A ,MESH: Pneumonia / physiopathology ,MESH: Pulmonary Surfactants / chemistry ,03 medical and health sciences ,Phospholipase A2 ,Internal medicine ,MESH: Severity of Illness Index ,medicine ,Animals ,030304 developmental biology ,MESH: Pulmonary Alveoli / physiopathology ,Lung ,business.industry ,Pulmonary Surfactants ,Pneumonia ,MESH: Bronchoalveolar Lavage Fluid / chemistry ,MESH: Phospholipases A / physiology ,MESH: Male ,Rats ,Pulmonary Alveoli ,Disease Models, Animal ,Phospholipases A2 ,Bronchoalveolar lavage ,Endocrinology ,030228 respiratory system ,biology.protein ,[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,MESH: Respiratory Distress Syndrome, Adult / etiology ,MESH: Disease Models, Animal ,business - Abstract
International audience; The aim of this study was to evaluate the presence of type-II secretory phospholipase A2 (sPLA2-IIA) in alveolar space and its possible role in the destruction of surfactant in three rat models of acute lung injury. Alveolar instillation of either lipopolysaccaride or live Pseudomonas aeruginosa resulted in a significant increase in lung oedema and in a decrease in static compliance of the respiratory system together with alveolar-neutrophil influx as compared with healthy control rats. The upregulation of messenger ribonucleic acid and sPLA2-IIA by the lung was evident. This was associated with surfactant degradation and a decrease in large:small ratio of surfactant aggregates in bacteria-instilled rats. A negative correlation between compliance and sPLA2-IIA activity in bronchoalveolar lavage fluid was shown. By contrast, during alpha naphthylthiourea-induced injury, neither alveolar-neutrophil influx nor increase in sPLA2-IIA activity was observed. Additional experiments in rats treated with a specific inhibitor of type-II secretory phospholipase A2 activity (3 acetamine-1-benzyl-2 ethylindolyl-5 oxy; propane phosphonic acid (LY311727)) demonstrated no improvement in physiological parameters despite a biochemical effect, suggesting that its activity is only one of the multiple factors involved in the pathophysiology of lung injury.
- Published
- 2003
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