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  • Title: Platelet-activating factor acetylhydrolase is increased in lung lavage fluid from patients with acute respiratory distress syndrome.
    Author: Grissom CK, Orme JF, Richer LD, McIntyre TM, Zimmerman GA, Elstad MR.
    Journal: Crit Care Med; 2003 Mar; 31(3):770-5. PubMed ID: 12626982.
    Abstract:
    OBJECTIVE: Platelet-activating factor (PAF) is a proinflammatory phospholipid that may contribute to inflammation in the acute respiratory distress syndrome (ARDS). PAF acetylhydrolase (PAF-AH) degrades PAF and regulates its biological activity. We characterized PAF-AH in bronchoalveolar lavage fluid from ARDS patients (n = 33, 22 survivors), patients at risk for ARDS (n = 6), and healthy controls (n = 6). DESIGN: Bronchoalveolar lavage was performed during acute (<96 hrs from onset), plateau (6 to 12 days), and late (> or = 14 days) phases of ARDS. PATIENTS: Intubated patients with ARDS or a risk factor for ARDS. MEASUREMENTS AND MAIN RESULTS: In ARDS, total bronchoalveolar lavage PAF-AH activity was markedly increased in the acute phase (87 +/- 89 mU/mL, n = 33) and then decreased in the plateau (23 +/- 14 mU/mL, n = 10) and late phases (19 +/- 14 mU/mL, n = 7) (p = .003). Total bronchoalveolar lavage PAF-AH activity during the acute phase of ARDS was also increased as compared with patients at risk for ARDS (16 +/- 13 mU/mL, n = 6) and healthy controls (3 +/- 3 mU/mL, n = 6) (p < .001). In contrast, plasma PAF-AH activities were the same in controls (3215 +/- 858 mU/mL, n = 6), in patients at risk for ARDS (3606 +/- 1607 mU/mL, n = 6), and during the acute phase of ARDS (3098 +/- 2395 mU/mL, n = 33) (p = .18). PAF-AH mRNA was present in alveolar macrophages in the acute phase of ARDS (five of six) and in at-risk patients (two of three) but not in healthy controls. CONCLUSIONS: PAF-AH activity is increased in bronchoalveolar lavage fluid from patients with ARDS. Likely sources include leakage of plasma PAF-AH into alveoli or release of PAF-AH from injured cells; however, the presence of PAF-AH mRNA in alveolar macrophages suggests that PAF-AH may be actively synthesized in the lungs of patients with ARDS. PAF-AH activity in the lungs of ARDS patients may regulate inflammation caused by PAF and related oxidized phospholipids generated in the inflammatory response.
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