White blood cell uses DNA 'catapult' to fight infection

August 14, 2008

Eosiniphils help prevent uncontrolled bacterial invasion

SALT LAKE CITY - U.S. and Swiss scientists have made a breakthrough in understanding how a type of white blood cell called the eosinophil may help the body to fight bacterial infections in the digestive tract, according to research published online this week in Nature Medicine.

Hans-Uwe Simon, from the University of Bern, Switzerland, Gerald J.Gleich, M.D., from the University of Utah School of Medicine, and their colleagues discovered that bacteria can activate eosinophils to release mitochondrial DNA in a catapult-like fashion to create a net that captures and kills bacteria.

"This is a fascinating finding," says Gleich, professor of dermatology and internal medicine at the University of Utah and a co-author of the study. "The DNA is released out of the cell in less than a second."

Eosiniphils, which comprise only 1 to 3 percent of human white blood cells, are known to be useful in the body's defense mechanisms against parasites. But their exact role in the immune system is not clear. Unlike other white blood cells, which are distributed throughout the body, eosinophils are found only in selected areas, including the digestive tract. Mitochondria - often referred to as the power plants of the cell - are components within cells that are thought to descend from ancient bacteria. Although most cellular DNA is contained in the nucleus, mitochondria have their own DNA.

Previous research has shown that eosinophils secrete toxic granule proteins during parasite infections and that these granule proteins kill bacteria. Simon, Gleich, and their colleagues found that when eosinophils are stimulated by infection, such as E. coli, they rapidly secrete mitochondrial DNA. This DNA binds to the granule proteins and forms a net that is able to trap and kill bacteria. The researchers also found higher levels of eosinophils were linked to improved survival and lower numbers of bacteria in the blood of mice with widespread bacterial infections.

The toxic proteins released by eosinophils are not always helpful to the body, however, and can damage nearby tissues. The inflammation in some types of asthma and Crohn's disease, a chronic inflammatory disease of the bowel, is attributed to eosinophils. In fact, Simon and his team first found evidence of these DNA-protein traps in tissue taken from the digestive tracts of people with Crohn's disease.

Earlier studies suggested another type of white blood cell - the neutrophil - also expels DNA and granule proteins to kill bacteria. However, this DNA comes from the nucleus and its release causes the neutrophil to die. The eosinophil is able to survive after expelling its mitochondrial DNA.

The researchers hope to learn more about how eosiniphils expel mitochondrial DNA. They speculate that the explosive mechanism might rely on stored energy, similar to the way plants release pollen into the air. "We don't know how eosinophils are capable of catapulting mitochondrial DNA so quickly," says Gleich.

Future investigation may focus on how this energy is generated and how this new knowledge can be applied to the treatment of bacterial infections and inflammatory diseases related to eosinophils.

University of Utah Health Sciences

Eosinophils: Structure, Biological Properties and Role in Disease
by Garry M. Walsh (Other Contributor)

The eosinophil is an enigmatic cell with a continuing ability to fascinate. In this book, experts in the field of eosinophil biology comprehensively update our knowledge on the human eosinophil in health and disease. Topics discussed include a synopsis of eosinophil characteristics, properties and role in disease. Important information on how eosinophils release their potent and toxic granule proteins will be covered and how these basic proteins give rise to pathologies including issues such as the function of the nerves.

Blood Cell Biochemistry, Volume 2: Megakaryocytes, Platelets, Macrophages, and Eosinophils (v. 2)
by J. Robin Harris (Editor)

Eosinophils in Allergy and Related Diseases: Workshop, Tokyo, June 2005, Proceedings (International Archives of Allergy and Immunology)
by S. Makino (Editor)

"International Archives of Allergy and Immunology" provides a forum for all areas of modern molecular and cellular allergology and immunology. The journal guarantees fast dissemination of significant, complete and novel work. All submitted manuscripts will be peer-reviewed by at least two independent referees, with every effort made to maintain review time as short as possible. In addition to original research papers the journal publishes short communications, reviews, minireviews, commentaries and opinions. This volume consists of the proceedings from the 13th Annual Workshop on Eosinophils in Allergy and Related Diseases, held in Tokyo in 2000. The presentations at the workshop cover all major topics in the field including the gene expression in eosinophil differentiation.

Eosinophils: A Comprehensive Review, and Guide to the Scientific and Medical Literature (Oxford Medical Publications)
by Christopher J. F. Spry (Author)

During the last decade there has been increased interest in the role of eosinophils in parasitic diseases, allergy, and other areas of clinical medicine. At the same time, cell biology and biochemical studies have shown how eosinophils respond, take part in inflammation, damage parasites, and can often harm normal cells, especially in the heart. This book describes what is known about these blood cells. Each section begins with a general review for the non-specialist reader and continues with a detailed assessment of current research, identifying areas where new knowledge has been acquired. Over 2,000 references are included, making this the most thorough review of the literature on these cells currently available.

Immunobiology of the Eosinophil: 1st: International Symposium Proceedings
by Takeshi Yoshida (Editor), Motomichi Torisu (Editor)

Eosinophils: Webster's Facts and Phrases
by Icon Group International (Author)

Ever need a fact or quotation on "eosinophils"? Designed for speechwriters, journalists, writers, researchers, students, professors, teachers, historians, academics, scrapbookers, trivia buffs and word lovers, this is the largest book ever created for this word. It represents a compilation of "single sentences" and/or "short paragraphs" from a variety of sources with a linguistic emphasis on anything relating to the term "eosinophils," including non-conventional usage and alternative meanings which capture ambiguities. This is not an encyclopedic book, but rather a collage of statements made using the word "eosinophils," or related words (e.g. inflections, synonyms or antonyms). This title is one of a series of books that considers all major vocabulary words. The entries in each book...

Eosinophil: Webster's Timeline History, 1921 - 2007
by Icon Group International (Author)

Webster's bibliographic and event-based timelines are comprehensive in scope, covering virtually all topics, geographic locations and people. They do so from a linguistic point of view, and in the case of this book, the focus is on "Eosinophil," including when used in literature (e.g. all authors that might have Eosinophil in their name). As such, this book represents the largest compilation of timeline events associated with Eosinophil when it is used in proper noun form. Webster's timelines cover bibliographic citations, patented inventions, as well as non-conventional and alternative meanings which capture ambiguities in usage. These furthermore cover all parts of speech (possessive, institutional usage, geographic usage) and contexts, including pop culture, the arts, social sciences...

Eosinophils: Webster's Timeline History, 1949 - 2007
by Icon Group International (Author)

Webster's bibliographic and event-based timelines are comprehensive in scope, covering virtually all topics, geographic locations and people. They do so from a linguistic point of view, and in the case of this book, the focus is on "Eosinophils," including when used in literature (e.g. all authors that might have Eosinophils in their name). As such, this book represents the largest compilation of timeline events associated with Eosinophils when it is used in proper noun form. Webster's timelines cover bibliographic citations, patented inventions, as well as non-conventional and alternative meanings which capture ambiguities in usage. These furthermore cover all parts of speech (possessive, institutional usage, geographic usage) and contexts, including pop culture, the arts, social...

Eosinophils, Allergy and Asthma
by A. Barry Kay (Editor)

The eosinophil is a type of white blood cell which plays a crucial role in the immunological defence mechanisms of the human body. Professor Kay has brought together an internationally respected group of doctors and scientists to produce a research level monograph which describes the recent advances in understanding which have placed the eosinophil at the centre of numerous pathophysiological mechanisms underlying allergy and asthma. This up to date, state of the art treatise includes chapters on the molecular biology and immunology of the eosinophil, the interactions of eosinophils with other blood elements and with the major immunological mediators in the body such as interleukin-5, platelet activating factor. There is also detailed coverage of the very latest advances in the...

Immunopharmacology of Eosinophils (Handbook of Immunopharmacology)
by H. Smith (Editor), R. M. Cook (Editor), Clive Page (Editor)

The eosinophil was identified more than a century ago, and at first dismissed as, at best, just another polymorphonuclear cell. Later, it was considered to play a pivotal role in countering the potentially damaging effects of mast cell degranulation via the production of neutralizing enzymes. Reappraisal followed with the demonstration of toxic effects of the eosinophil's cationic proteins. Instead of a cell with predominantly beneficial properties, the eosinophil was seen as actively contributing to the pathogeneisis of chronic inflammatory diseases such as asthma.