Structural similarities between
apolipoprotein(a) (
apo(a)), the unique
apoprotein of
lipoprotein(a), and
plasminogen, the
zymogen of
plasmin, can interfere with functions of
plasmin (
ogen) in vitro. The purpose of this study was to evaluate the role of
apo(a) in
inflammation in vivo using
apo(a) transgenic mice and to determine if effects are
plasminogen-dependent using backgrounds that are either
plasminogen-replete or
plasminogen-deficient. After administration of peritoneal inflammatory stimuli, thioglycollate, bioimplants or
lipopolysaccharide, the number of responding peritoneal neutrophils and macrophages were quantified.
Apo(a), in either wild-type or
plasminogen deficient backgrounds, inhibited neutrophil recruitment but had no effect on
plasminogen-dependent macrophage recruitment. Macrophage-inflammatory protein-2, a neutrophil
chemokine, was reduced in
apo(a) mice, and injection of this
chemokine prior to thioglycollate restored neutrophil recruitment in
apo(a) transgenic mice. In the
lipopolysaccharide model, mice with
apo(a), unlike mice without
apo(a), did not increase neutrophil recruitment in response to the stimulus. In the bioimplant model, neutrophil recruitment and neutrophil
cytokines were reduced in
apo(a)tg mice but only in a
plasminogen-deficient background. These results indicate for the first time that
apo(a), independent of
plasminogen interaction, inhibits neutrophil recruitment in vivo in diverse peritoneal inflammatory models. Hence,
apo(a) may function as a cell specific suppressor of the inflammatory response.