Cell-specific modulation of surfactant proteins by ambroxol treatment.
Ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanole hydrochloride], a mucolytic agent, was postulated to provide surfactant stimulatory properties and was previously used to prevent surfactant deficiency. Currently, the underlying mechanisms are not exactly clear. Because surfactant homeostasis is regulated by surfactant-specific proteins (SP), we analyzed protein amount and mRNA expression in whole lung tissue, isolated type II pneumocytes and bronchoalveolar lavage of Sprague-Dawley rats treated with ambroxol i.p. (75 mg/kg body weight, twice a day [every 12 h]). The methods used included competitive polymerase chain reaction (RT-PCR), Northern blotting, Western immunoblotting, and immunohistochemistry. In isolated type II pneumocytes of ambroxol-treated animals, SP-C protein and mRNA content were increased, whereas SP-A, -B and -D protein, mRNA, and immunoreactivity remained unaffected. However, ambroxol treatment resulted in a significant increase of SP-B and in a decrease of SP-D in whole lung tissue with enhanced immunostaining for SP-B in Clara Cells. SP-A and SP-D were significantly decreased in BAL fluid of ambroxol-treated animals. The data suggest that surfactant protein expression is modulated in a cell-specific manner by ambroxol, as type II pneumocytes exhibited an increase in SP-C, whereas Clara cells exhibited an increase in the immunoreactivity for SP-B accounting for the increased SP-B content of whole lung tissue. The results indicate that ambroxol may exert its positive effects, observed in the treatment of diseases related to surfactant deficiency, via modulation of surfactant protein expression.
Seifart
Carola
C
Department of Internal Medicine, Division of Respiratory Medicine, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg, Germany. zwiebel@mailer.uni-marburg.de
Clostermann
Ursula
U
Seifart
Ulf
U
Müller
Bernd
B
Vogelmeier
Claus
C
von Wichert
Peter
P
Fehrenbach
Heinz
H
D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D005100:Expectorants / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005100:Expectorants; D037661:Pulmonary Surfactant-Associated Proteins; D012333:RNA, Messenger; D000551:Ambroxol