Platelet-activating factor acetylhydrolase is increased in lung lavage fluid from patients with acute respiratory distress syndrome.
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).


METHODS
Bronchoalveolar lavage was performed during acute (<96 hrs from onset), plateau (6 to 12 days), and late (> or = 14 days) phases of ARDS.


METHODS
Intubated patients with ARDS or a risk factor for ARDS.


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.
Grissom
Colin K
CK
Pulmonary and Critical Care Division, Department of Internal Medicine, LDS Hospital, Salt Lake City, UT, USA.
Orme
James F
JF
Richer
Lori D
LD
McIntyre
Thomas M
TM
Zimmerman
Guy A
GA
Elstad
Mark R
MR
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001999:Bronchoscopy; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007249:Inflammation; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010741:Phospholipases A / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012128:Respiratory Distress Syndrome / Q000201:enzymology* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors
D012333:RNA, Messenger; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase