Polarized secretion of fibrinogen by lung epithelial cells.

Abstract:

:The lung epithelium has recently been identified as a novel site of fibrinogen (FBG) biosynthesis. A coordinated upregulation of A alpha, B beta, and gamma chain FBG gene transcription occurs upon stimulation of A549 lung epithelial cells with dexamethasone (DEX) and the proinflammatory mediator interleukin-6 (IL-6). Subsequently, the cells synthesize and secrete fully assembled FBG. This study addresses the polarity of such FBG secretion by A549 cells cultured on polycarbonate membrane filters. After induction with IL-6 and DEX, cells were metabolically labeled, and FBG was immunopurified from the apical and basolateral chambers. Analysis by gel electrophoresis revealed that A549 cells secreted newly synthesized FBG in a polarized manner, with the majority (80%) of FBG secreted basolaterally. Consistent with this observation, immunoelectron microscopy using Protein A-gold labeling showed FBG within 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 basolateral component of secretion, causing intracellular retention of FBG. These data provide evidence that FBG is secreted by lung alveolar epithelial cells vectorially toward the basement membrane, which may reflect in vivo processes associated with local injury, inflammation, and repair mechanisms.

authors

Guadiz G,Sporn LA,Goss RA,Lawrence SO,Marder VJ,Simpson-Haidaris PJ

doi

10.1165/ajrcmb.17.1.2730

subject

Has Abstract

pub_date

1997-07-01 00:00:00

pages

60-9

issue

1

eissn

1044-1549

issn

1535-4989

journal_volume

17

pub_type

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