Targeted transgenic expression of beta(2)-adrenergic receptors to type II cells increases alveolar fluid clearance.
Clearance of edema fluid from the alveolar space can be enhanced by endogenous and exogenous beta-agonists. To selectively delineate the effects of alveolar type II (ATII) cell beta(2)-adrenergic receptors (beta(2)-ARs) on alveolar fluid clearance (AFC), we generated transgenic (TG) mice that overexpressed the human beta(2)-AR under control of the rat surfactant protein C promoter. In situ hybridization showed that transgene expression was consistent with the distribution of ATII cells. TG mice expressed 4.8-fold greater beta(2)-ARs than nontransgenic (NTG) mice (939 +/- 113 vs. 194 +/- 18 fmol/mg protein; P < 0.001). Basal AFC in TG mice was approximately 40% greater than that in untreated NTG mice (15 +/- 1.4 vs. 10.9 +/- 0.6%; P < 0.005) and approached that of NTG mice treated with the beta-agonist formoterol (19.8 +/- 2.2%; P = not significant). Adrenalectomy decreased basal AFC in TG mice to 9.7 +/- 0.5% but had no effect on NTG mice (11.5 +/- 1.0%). Na(+)-K(+)-ATPase alpha(1)-isoform expression was unchanged, whereas alpha(2)-isoform expression was approximately 80% greater in the TG mice. These findings show that beta(2)-AR overexpression can be an effective means to increase AFC in the absence of exogenous agonists and that AFC can be stimulated by activation of beta(2)-ARs specifically expressed on ATII cells.
McGraw
D W
DW
Department of Medicine, University of Cincinnati College of Medicine, OH 45267, USA.
Fukuda
N
N
James
P F
PF
Forbes
S L
SL
Woo
A L
AL
Lingrel
J B
JB
Witte
D P
DP
Matthay
M A
MA
Liggett
S B
SB
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015139:Blotting, Southern; D001826:Body Fluids / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011650:Pulmonary Alveoli / Q000254:growth & development / Q000378:metabolism*; D011654:Pulmonary Edema / Q000378:metabolism* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase