Reduced in vivo plasma fibronectin content of the lung matrix
during post-operative sepsis.
Rebres, Robert A., Eshin Cho, Robert F. Rotundo, and Thomas M. Saba.
Department of Physiology and Cell Biology, Neil Hellman Medical
Research Building, Albany Medical College, Albany, New York 12208
APStracts 3:0075L, 1996.
Sepsis following surgery, trauma or burn and the associated release of
cytokines from inflammatory cells appears to contribute to altered
lung endothelial permeability and respiratory failure. Fibronectin
(Fn), an opsonic and adhesive glycoprotein, exists in both a soluble
form in plasma and an insoluble form in the extracellular matrix
(ECM). Recent studies (Am. J. Physiol. 265:L148-L157, 1993) suggest
that the ECM content of Fn may be a factor influencing lung
microvascular permeability. We evaluated the incorporation of plasma
-derived Fn (pFn) into the ECM of various tissues including the lung
during post-operative sepsis in the rat using intravenously infused
purified rat 125I-Fn. Sham-operated non-septic rats were compared to
post-operative septic rats using a model of laparotomy followed by
cecal ligation and puncture. To label the plasma Fn pool, rats
received i.v. 3 [mu]g of purified 125I-Fn/100 gm body weight 6 h
after surgery. Matrix content of 125I-Fn in tissues was assessed by
its relative solubility deoxycholate (DOC) detergent, since DOC
insoluble Fn reflects matrix incorporated Fn. Tissue 125I-Fn in the
DOC soluble and insoluble fractions was determined at 4 h post-125I
-Fn infusion. Septic rats exhibited a peripheral leukopenia as well as
reduction in plasma volume, Fn half life, and total pFn pool.
Incorporation of pFn in the liver and spleen of post-surgical septic
rats was not different (p>0.05) from sham rats, but
incorporation was significantly decreased in the lung (p<0.05).
However, lung tissue harvested from septic or sham rats demonstrated
no difference in its ability to incorporate soluble 125I-pFn into the
ECM under controlled in vitro conditions. Pulse chase experiments
with lung tissue from sham or septic rats also revealed similar rates
of retention/turnover of ECM 125I-Fn. These data suggest that the in
vivo inflammatory environment in the lung during post-operative
sepsis, which cannot be reproduced in vitro, may alter the Fn content
of the ECM of the lung. Such reduced levels of pFn into the lung ECM
may be a factor influencing lung vascular integrity during post
-operative sepsis.
Received 16 January 1996; accepted in final form 2 May 1996.
APS Manuscript Number L21-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 May 96