Am J Physiol Lung Cell Mol Physiol 2003 Feb;284(2):L402-9
Haptoglobin reduces lung injury associated with exposure to blood.
Yang F, Haile DJ, Berger FG, Herbert DC, Van Beveren E, Ghio AJ.
Departments of Cellular and Structural Biology and Medicine,
University
of Texas Health Science Center, San Antonio, Texas 78229;
Department of Biological Sciences, University of South Carolina,
Columbia,
South Carolina 29208.
The biological functions of the acute- phase protein haptoglobin
(Hp)
may be related to its ability to bind hemoglobin (Hb) or to
modulate immune response. Hp is expressed at a high level in lung
cells,
yet its protective role(s) in the lung is not known. With the use of
transgenic
mice overexpressing Hp in alveolar macrophages, we demonstrated that Hp
diminished Hb-induced lung injury when the lung was exposed to whole
blood.
In transgenic mouse lungs, Hb was more efficiently removed, and the
induction
of stress- responsive heme oxygenase-1 gene was significantly lower
when
compared with wild-type mice. At 24 h after blood treatment, the
ferritin
level that serves as an index for intracellular iron content was also
lower
in alveolar macrophages in transgenic mice than in wild-type mice. We
propose
that an Hp-mediated Hb catabolism process exists in alveolar
macrophages.
This process is likely coupled to an iron mobilization pathway and may
be an efficient mechanism to reduce oxidative damage associated with
hemolysis.