Although the liver is the primary site of fibrinogen (FBG) synthesis,
epithelial cells from diverse tissues have been shown to express one o
r more of the FBG A alpha, B beta, and gamma chain genes. In contrast,
marrow megakaryocytes, which store FBG in the alpha-granules, are tho
ught not to express the FBG genes. Our earlier studies have shown that
epithelial cells in a variety of extrahepatic tissues express the gam
ma chain gene ubiquitously, while the mRNAs for the A alpha and B beta
chain genes are essentially undetectable. During systemic inflammatio
n, the liver secretes increased levels of FBG into the circulation, an
d lung epithelium responds to local inflammation during pulmonary infe
ction by increased transcription of the gamma-FBG gene. Therefore, to
determine whether extrahepatic epithelial cells express the A alpha, B
beta, and gamma chain genes in response to proinflammatory mediators,
cultured lung epithelial cells were treated with interleukin-6 (IL-6)
and dexamethasone (DEX). Northern blot analysis demonstrated that the
levels of gamma-FBG mRNA in cultured lung (A549) and liver (HepG2) ep
ithelial cells increased 2- to 10-fold in response to treatment. Rever
se-transcriptase-polymerase chain reaction amplification demonstrated
increased accumulation of steady state levels of FBG A alpha, B beta,
and gamma chain mRNAs in lung epithelial cells after treatment. The ba
sal level of lung cell gamma-FBG gene transcription was not accompanie
d by appreciable levels of A alpha and B beta chain gene transcription
; however, nuclear run-on analysis suggested that the increase in lung
cell FBG mRNAs in response to DEX +/- IL-6 was due to new transcripti
on. Furthermore, stimulation of lung epithelial cells with IL-6 + DEX
resulted in maximal secretion of intact FBG (340 kD) composed of the c
haracteristic A alpha, B beta, and gamma chain polypeptides. The data
suggest that basal expression of the gamma-FBG gene in extrahepatic ti
ssue occurs ubiquitously in the absence of detectable levels of A alph
a- and B beta-FBG gene expression, which are then upregulated on induc
tion of an inflammatory response. This would result in local synthesis
and secretion of FBG in the injured tissue, supporting the hypothesis
that production of FBG by extrahepatic epithelial cells in response t
o inflammation plays a role in wound repair. (C) 1997 by The American
Society of Hematology.