Secretory phospholipases A2 stimulate mucus secretion, induce airway inflammation, and produce secretory hyperresponsiveness to neutrophil elastase in ferret trachea.
Secretory phospholipases A(2) (sPLA(2)) are increased in the bronchoalveolar lavage fluid of patients with asthma and acute respiratory distress syndrome. Intratracheal sPLA(2) instillation induces acute lung injury in the rat and guinea pig. We hypothesized that sPLA(2) would stimulate mucus secretion in vitro and that intratracheal sPLA(2) exposure would induce mucus hypersecretion and airway inflammation in the ferret trachea in vivo. In vitro, porcine pancreatic sPLA(2) at a concentration of 0.5 or 5 U/ml significantly increased mucous glycoconjugate (MG) secretion from the excised ferret trachea. P-bromophenacylbromide (a sPLA(2) inhibitor), quercetin (a lipoxygenase inhibitor), or MK-886 (a 5-lipoxygenase inhibitor), each at 10(-4) M, significantly reduced sPLA(2)-induced MG secretion. sPLA(2)-stimulated MG secretion was decreased in Ca(2+)-free medium. In vivo, ferrets were intubated for 30 min once per day for 3 days using an ETT coated with 20 units of porcine pancreatic sPLA(2) mixed in water-soluble jelly. Constitutive MG secretion increased 1 day after sPLA(2) exposure and returned to control 5 days later. Human neutrophil elastase (HNE) at 10(-8) M increased MG secretion in the sPLA(2)-exposed trachea compared with that in the control trachea, but methacholine at 10(-7) M did not. sPLA(2)-induced secretory hyperresponsiveness continued for at least 5 days after sPLA(2) exposure ended. sPLA(2) increased tracheal inflammation, MG secretion, and secretory hyperresponsiveness to HNE probably through enzymatic action rather than by activation of its receptor.
Okamoto
Kosuke
K
Department of Pediatrics, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1081, USA.
Kim
Jung-Soo
JS
Rubin
Bruce K
BK
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D005289:Ferrets; D006001:Glycoconjugates / Q000378:metabolism; D054501:Group II Phospholipases A2; D006801:Humans; D066298:In Vitro Techniques; D019272:Leukocyte Elastase / Q000633:toxicity*; D008297:Male; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D010741:Phospholipases A / Q000633:toxicity*; D012128:Respiratory Distress Syndrome / Q000503:physiopathology; D013552:Swine; D014132:Trachea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
D006001:Glycoconjugates; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D019272:Leukocyte Elastase