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.