Effects of perfluorocarbons on surfactant exocytosis and membrane properties in isolated alveolar type II cells.
BACKGROUND
Perfluorocarbons (PFC) are used to improve gas exchange in diseased lungs. PFC have been shown to affect various cell types. Thus, effects on alveolar type II (ATII) cells and surfactant metabolism can be expected, data, however, are controversial.


OBJECTIVE
The study was performed to test two hypotheses: (I) the effects of PFC on surfactant exocytosis depend on their respective vapor pressures; (II) different pathways of surfactant exocytosis are affected differently by PFC.


METHODS
Isolated ATII cells were exposed to two PFC with different vapor pressures and spontaneous surfactant exocytosis was measured. Furthermore, surfactant exocytosis was stimulated by either ATP, PMA or ionomycin. The effects of PFC on cell morphology, cellular viability, endocytosis, membrane permeability and fluidity were determined.


RESULTS
The spontaneous exocytosis was reduced by PFC, however, the ATP and PMA stimulated exocytosis was slightly increased by PFC with high vapor pressure. In contrast, Ionomycin-induced exocytosis was decreased by PFC with low vapor pressure. Cellular uptake of FM 1-43 - a marker of membrane integrity - was increased. However, membrane fluidity, endocytosis and viability were not affected by PFC incubation.


CONCLUSIONS
We conclude that PFC effects can be explained by modest, unspecific interactions with the plasma membrane rather than by specific interactions with intracellular targets.
Wemhöner
Andreas
A
University Hospital Dresden, Department for Pediatric Intensive Care and Neonatology, Technical University Dresden, Germany.
Hackspiel
Irmgard
I
Hobi
Nina
N
Ravasio
Andrea
A
Haller
Thomas
T
Rüdiger
Mario
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects*; D005466:Fluorocarbons / Q000494:pharmacology*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D055548:Vapor Pressure
D005466:Fluorocarbons; D037661:Pulmonary Surfactant-Associated Proteins; C008805:perfluorodecalin; D015759:Ionomycin; D000255:Adenosine Triphosphate; D013755:Tetradecanoylphorbol Acetate; C003073:perfluoromethylcyclohexane
Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1043-8
18359887
Am J Respir Cell Mol Biol. 2000 Apr;22(4):441-50
10745025
N Engl J Med. 1996 Sep 12;335(11):761-7
8778584
Biochim Biophys Acta. 1987 Jul 10;901(1):138-46
3593721
Comp Biochem Physiol A Mol Integr Physiol. 2001 May;129(1):233-43
11369548
J Appl Physiol (1985). 2001 Nov;91(5):1941-7
11641328
Am J Physiol Lung Cell Mol Physiol. 2001 May;280(5):L991-8
11290524
Am J Respir Cell Mol Biol. 2006 Jun;34(6):677-87
16439800
J Cell Biol. 2001 Oct 15;155(2):279-89
11604423
Biochim Biophys Acta. 1995 Mar 22;1234(2):197-202
7696294
Crit Care Med. 1996 Jul;24(7):1252-6
8674344
J Biol Phys. 2003 Dec;29(4):363-99
23345856
Respir Res. 2007 Jun 05;8:40
17550584
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1579-84
9465058
J Crit Care. 1999 Jun;14(2):84-92
10382789
J Biomol Screen. 2006 Apr;11(3):286-95
16699129
Chest. 1970 Mar;57(3):263-5
5417668
J Appl Physiol (1985). 1990 Aug;69(2):465-72
2121700
J Pharm Sci. 2008 Aug;97(8):3195-206
17990311
Am J Physiol Lung Cell Mol Physiol. 2000 May;278(5):L1008-17
10781432
Biochim Biophys Acta. 1978 Dec 15;515(4):367-94
365237
Crit Care Med. 2001 Sep;29(9):1786-91
11546986
Crit Care Med. 1998 Oct;26(10):1707-15
9781729
Am J Physiol Lung Cell Mol Physiol. 2000 May;278(5):L1018-24
10781433
BMC Cell Biol. 2008 Jun 24;9:34
18577212
Curr Opin Neurobiol. 1996 Jun;6(3):365-71
8794083
Biochim Biophys Acta. 2007 Oct;1771(10):1308-18
17765009
Fed Proc. 1970 Sep-Oct;29(5):1813-5
5457592
Am Rev Respir Dis. 1986 Jul;134(1):141-5
3637065
Chest. 1974 Jul;66(1 Suppl):29S-30S
4495151
Crit Care Med. 2003 Apr;31(4):1190-6
12682492
News Physiol Sci. 2001 Oct;16:239-43
11572929
Annu Rev Physiol. 2005;67:595-621
15709972
J Appl Physiol (1985). 1989 May;66(5):2039-44
2745272