Apolipoprotein(a): A natural regulator of inflammation

Dec 24, 2008

In a study to be published in the January 09 issue of Experimental Biology and Medicine, Hoover-Plow and co-workers in seeking to define a role of apo(a) in leukocyte recruitment have identified a novel activity of apo(a) apolipoprotein that may function as a natural and cell specific suppressor of the inflammatory response in vivo. In addition, a mechanism for this novel function of apo(a) was also identified: its selective regulation of cytokine production. These effects of apo(a) are independent of its molecular mimicry of Plg.

Lipoprotein(a) (Lp(a)) is similar to low density lipoprotein (LDL), but contains an additional apolipoprotein, apo(a). Numerous clinical studies conducted over the past 40 years have identified Lp(a) as a risk factor independent from LDL for a variety of cardiovascular pathologies. Much of the focus of apo(a) pathogenic activities has centered on its strong resemblance to plasminogen, the zymogen for plasmin, the primary enzyme for blood clot degradation. In addition to its important role in clot lysis, plasmin is required for leukocyte recruitment in inflammation. While several in vitro studies have demonstrated the interference of apo(a) in plasminogen leukocyte recruitment, evidence for this in vivo has been lacking.

In vivo investigation of Lp(a) function has been impeded by the lack of availability of small animal models. Lp(a) is expressed only in humans, nonhuman primates and the European hedgehog. In this study Hoover-Plow's group utilized mice with apo(a) in a plasminogen deficient or replete background to study leukocyte recruitment in three models of inflammation. Hoover-Plow said "In this study apo(a) impeded neutrophil recruitment in two of the models of inflammation, thioglycollate and lipopolysaccharide induced peritonitis. Apo(a) also inhibited neutrophil chemoattractants, and neutrophil recruitment was restored in mice administered neutrophil chemoattractants.

The impaired neutrophil recruitment occurred by a mechanism independent of plasminogen. While the clinical studies point to pathogenic functions of apo(a), a physiological role of Lp(a) has been elusive, but must exist to account for its role in humans and non-human primates, but not most other species. Our results indicate for the first time that apo(a), independent of plasminogen interaction, inhibits neutrophil recruitment in vivo and functions as a cell specific suppressor of the inflammatory response."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said "Hoover-Plow and colleagues have demonstrated a novel role for apo(a) as a regulator of inflammation. This represents an important contribution to our understanding of the regulation of neutrophil recruitment during the inflammatory response". Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences.

Source: Society for Experimental Biology and Medicine

Explore further: Scientists discover new clues to how weight loss is regulated

add to favorites email to friend print save as pdf

Related Stories

Review: Apple Pay in action

2 minutes ago

If there ever comes a day I can ditch my wallet and use my phone to pay for everything, I'll look back to my first purchase through Apple Pay: a Big Mac and medium fries for $5.44. That wallet-free day won't ...

Samsung seeks boost from redesigned Note

9 minutes ago

The latest version of Samsung's popular big-screen Galaxy Note has gone on sale at a crucial time for the South Korean company as it suffers a rapid decline in profit from its global smartphone business.

Pharmaceuticals and the water-fish-osprey food web

9 hours ago

Ospreys do not carry significant amounts of human pharmaceutical chemicals, despite widespread occurrence of these chemicals in water, a recent U.S. Geological Survey (USGS) and Baylor University study finds. ...

Recommended for you

Team finds key signaling pathway in cause of preeclampsia

6 hours ago

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

10 hours ago

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments : 0