title: Role of actin depolymerization in the surfactant secretory response of alveolar epithelial type II cells.
abstract: Alveolar epithelial type II cells (AET2) respond with exocytosis of surfactant containing lamellar bodies to stimulation with mechanical stretch and secretagogues, a process that is fundamental for maintaining alveolar stability and lung gas exchange. In the present study in cultured rat AET2, we employed botulinum C2 toxin, a binary toxin which ADP ribosylates nonmuscle G-actin, as a specific tool to probe the role of the actin microfilament system in the surfactant secretory process. Incubation of AET2 with C2 toxin caused a dose-dependent decay of the cellular F-actin content to a minimum of 20% of baseline, concomitant with an increase in monomeric actin. In parallel, a significant augmentation of baseline surfactant secretion up to twofold elevated levels above control was noted, as assessed by the release of prelabeled phosphatidylcholine. Pretreatment with phalloidin, which stabilized F-actin and reduced the level of G-actin, prevented the C2 toxin-elicited enhancement of baseline surfactant secretion. Even low C2 toxin concentrations, resulting in a reduction of total cellular F-actin content of approximately 10%, sufficed to augment secretagogue (ATP) and, more impressively, mechanical stress elicited an increase in surfactant secretion; the response to the biophysical challenge more than doubled. When investigated in the absence of toxin, different secretagogues (ATP, phorbol ester, betamimetics) caused a rapid-onset, transient reduction of F-actin in the range between 15 and 25% as a consistent part of their secretory response pattern. These data suggest that the state of actin polymerization is intimately linked to the exocytosis process underlying surfactant secretion in AET2. Microfilament system-related compartmentalization effects and/or or the impact of the state of actin assembly on signaling events may be considered as underlying events.
authors.affiliation: Department of Internal Medicine and Institute of Clinical Chemistry and Pathobiochemistry, Justus-Liebig-University, Giessen. Freiburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Rose
authors.forename: C
authors.initials: C
authors.lastname: Kürth-Landwehr
authors.forename: U
authors.initials: U
authors.lastname: Sibelius
authors.forename: K H
authors.initials: KH
authors.lastname: Reuner
authors.forename: K
authors.initials: K
authors.lastname: Aktories
authors.forename: W
authors.initials: W
authors.lastname: Seeger
authors.forename: F
authors.initials: F
authors.lastname: Grimminger
mesh_terms: D000199:Actins / Q000378:metabolism*; D000328:Adult; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D008297:Male; D010590:Phalloidine / Q000494:pharmacology; D010812:Physical Stimulation; D011108:Polymers / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
chemical_list: D000199:Actins; D011108:Polymers; D011663:Pulmonary Surfactants; D010590:Phalloidine; D001905:Botulinum Toxins; C096324:botulinum toxin type C