G. Guadiz et al., POLARIZED SECRETION OF FIBRINOGEN BY LUNG EPITHELIAL-CELLS, American journal of respiratory cell and molecular biology, 17(1), 1997, pp. 60-69
The lung epithelium has recently been identified as a novel site of fi
brinogen (FBG) biosynthesis. A coordinated upregulation of A alpha, B
beta, and gamma chain FBG gene transcription occurs upon stimulation o
f A549 lung epithelial cells with dexamethasone (DEX) and the proinfla
mmatory mediator interleukin-6 (IL-6). Subsequently, the cells synthes
ize and secrete fully assembled FBC. This study addresses the polarity
of such FBG secretion by A549 cells cultured on polycarbonate membran
e filters. After induction with IL-6 and DEX, cells were metabolically
labeled, and FBG was immunopurified from the apical and basolateral c
hambers. Analysis by gel electrophoresis revealed that A549 cells secr
eted newly synthesized FBG in a polarized manner, with the majority (8
0%) of FBG secreted basolaterally. Consistent with this observation, i
mmunoelectron microscopy using Protein A-gold labeling showed FBG with
in secretory vesicles in close proximity to the basolateral aspect of
the A549 cell membrane. Polarized secretion was microtubule-dependent
since depolymerization using colchicine significantly reduced the baso
lateral component of secretion, causing intracellular retention of FBG
. These data provide evidence that FBG is secreted by lung alveolar ep
ithelial cells vectorially toward the basement membrane, which may ref
lect in vivo processes associated with local injury, inflammation, and
repair mechanisms.