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: 3-D human skin maps aid study of relationships between molecules, microbes and environment

Related Stories

New thesis maps the origin of colour vision

14 minutes ago

Roughly 500 million years ago, the genome of vertebrate animals' early ancestors doubled in size, not just once but twice. This meant that suddenly there were several gene copies which were free to develop new functions. ...

Researcher focuses on US suburban housing equity

24 minutes ago

Since the 1968 Fair Housing act was passed, have housing opportunities for people of color improved? Did the Great Recession beginning in 2007 stop or slow progress toward better housing for people of color?

Engineering students use sound waves to put out fires

14 minutes ago

Two engineering students at George Mason University have found a way to use sound waves to quash fires and have built a type of extinguisher using what they have learned that they hope will revolutionize ...

Cash remains king in Chile but its days could be numbered

35 minutes ago

For more than a year now, Chileans have endured a crisis of cash access. Despite global moves toward new forms of payment such as contactless and mobile transfers, the crisis in Chile highlights the continuing ...

Recommended for you

Protein may improve liver regeneration

4 hours ago

Researchers at UC Davis have illuminated an important distinction between mice and humans: how human livers heal. The difference centers on a protein called PPARα, which activates liver regeneration. Normally, mouse PPARα ...

Female embryos less likely to survive to birth

13 hours ago

New research has challenged the prevailing belief that the higher proportion of male babies born in the general population results from a higher proportion of males being conceived. 

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.