title: Liver carboxylesterase cleaves surfactant protein (SP-) B and promotes surfactant subtype conversion.
abstract: Conversion of the biophysically active large surfactant aggregate subtype of alveolar surfactant into the less surface active small surfactant aggregates occurs in vitro and in vivo, possibly in dependency of a carboxylesterase, entitled surfactant convertase. The substrate has yet not been safely identified. Utilizing the in vitro cycling assay we investigated conversion of an organic rabbit lavage extract reconstituted with SP-A. Porcine liver carboxylesterase, which is closely related to surfactant convertase, induced subtype conversion to a similar degree as compared with native lavage fluid containing endogenous convertase. In addition, we asked for cleavage products of SP-B and identified a approximately 12 kDa band upon cycling with liver carboxylesterase, having the same N-terminus as mature SP-B. A band of same molecular weight was found in native lavage fluid after in vitro conversion mediated by the endogenous convertase. We conclude that SP-B plays a pivotal role during subtype conversion and represents the substrate for surfactant convertase.
authors.affiliation: University of Giessen Lung Center (UGLC), Department of Internal Medicine, Medical Clinic II, Justus-Liebig University, Giessen, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Ruppert
authors.forename: Ariane
authors.initials: A
authors.lastname: Bagheri
authors.forename: Philipp
authors.initials: P
authors.lastname: Markart
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Andreas
authors.initials: A
authors.lastname: Günther
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D043182:Carboxylesterase / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D008099:Liver / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D011817:Rabbits
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D043182:Carboxylesterase