Featured Research

from universities, journals, and other organizations

Aspirin Targets Key Cell That Triggers Organ Rejection And Other Immune Responses, Report University Of Pittsburgh Researchers

Date:
June 25, 2001
Source:
University Of Pittsburgh Medical Center
Summary:
University of Pittsburgh researchers have identified a new cellular target for aspirin, shedding light on the mechanisms of the most widely used drug in the world and raising a set of intriguing questions, including whether aspirin could be useful for preventing organ rejection.

PITTSBURGH, June 5 -- University of Pittsburgh researchers have identified a new cellular target for aspirin, shedding light on the mechanisms of the most widely used drug in the world and raising a set of intriguing questions, including whether aspirin could be useful for preventing organ rejection.

In the June 15 issue of the Journal of Immunology, the researchers report for the first time that aspirin has a profound effect on bone-marrow derived dendritic cells -- the powerful immune system cells that are responsible for initiating an immune response -- by preventing their maturation and hence, their ability to signal other cells to attack.

The findings help to explain why aspirin taken in high doses significantly reduces inflammation and provides relief to patients with various autoimmune diseases, including arthritis and rheumatic fever, says lead author Holger Hackstein, M.D., a visiting research fellow at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute, who is working in the lab of Angus Thomson, Ph.D., D.Sc., professor of surgery and molecular genetics and biochemistry and senior author on the paper.

And while the research used a mouse model to look at aspirin's effect on myeloid dendritic cells, the findings point to possible novel therapies for patients with autoimmune diseases as well as approaches that could induce tolerance in organ transplant recipients. The researchers plan a series of animal studies to determine if aspirin can help prevent organ rejection. Specifically, they will be looking to see what role aspirin has in preventing dendritic cells from calling in the troops of T and B lymphocytes that directly attack transplanted organs.

"These findings provide new insight into the immunopharmacology of aspirin. Moreover, exposure to this readily available drug provides a simple, inexpensive and highly effective means to manipulate the immunostimulatory capacity of dendritic cells," wrote the authors.

"While these results are very intriguing, it would be premature to advise patients to ingest large quantities of aspirin. For many transplant patients, this could be medically dangerous,” warns Dr. Hackstein, whose primary appointment is with the Institute of Clinical Immunology and Transfusion Medicine at Justus-Liebig University of Giessen in Giessen, Germany.

Dendritic cells are rare immune system cells that originate in bone marrow and are present in all tissue. Myeloid dendritic cells initiate immune system attack, whereas lymphoid-related dendritic cells are believed to temper the immune system, according to other studies performed by Dr. Thomson and colleagues. Essentially, myeloid dendritic cells initiate an immune response by recognizing something that is foreign and then calling out signals that serve to present the foreign antigen to other immune system cells that do their part to destroy it.

Despite its discovery more than 100 years ago, little is known about how aspirin actually works to control pain and inflammation, or how it is beneficial for patients with autoimmune diseases. What is known is that it acts on two pathways, one involving prostaglandins, and the other, a more recent discovery, involving nuclear factor –K(kappa)B (NF-KB). Aspirin inhibits the activation of NF-KB, molecules that activate chemicals to trigger inflammation. More specifically, according to the Pittsburgh team, aspirin disables NF-KB inside dendritic cells.

Without NF-KB activation, the dendritic cells are hindered from performing the normal function of a mature cell. They no longer have the capability to place molecular signals on the outside of their cells that serve as warnings to the T and B cells that an attack is warranted against a transplanted organ, or in the case of autoimmune disease, a patient's own tissue. The potential for an immune response is stopped in its tracks.

The researchers also found aspirin to have a surprising effect on the precursor or progenitor dendritic cells. They assumed that if aspirin inhibited maturation of normal dendritic cells that it would prevent their development altogether when progenitor cells were exposed to aspirin. Instead, aspirin enabled the robust production of pure dendritic cells that remained immature, never developing the capacity to present antigens.

Among other things, this finding proves that aspirin does not have a toxic effect on dendritic cells, the authors note.

In addition to Drs. Hackstein and Thomson, other authors include Adrian E. Morelli, M.D., Ph.D.; Adriana T. Larregina, M.D., Ph.D.; Raymond W. Ganster, Ph.D.; Glenn D. Papworth, Ph.D.; Alison J. Logar, B.S.; Simon C. Watkins, Ph.D.; and Louis D. Falo, M.D., Ph.D. The research was supported by grants from the National Institutes of Health.


Story Source:

The above story is based on materials provided by University Of Pittsburgh Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pittsburgh Medical Center. "Aspirin Targets Key Cell That Triggers Organ Rejection And Other Immune Responses, Report University Of Pittsburgh Researchers." ScienceDaily. ScienceDaily, 25 June 2001. <www.sciencedaily.com/releases/2001/06/010605080118.htm>.
University Of Pittsburgh Medical Center. (2001, June 25). Aspirin Targets Key Cell That Triggers Organ Rejection And Other Immune Responses, Report University Of Pittsburgh Researchers. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2001/06/010605080118.htm
University Of Pittsburgh Medical Center. "Aspirin Targets Key Cell That Triggers Organ Rejection And Other Immune Responses, Report University Of Pittsburgh Researchers." ScienceDaily. www.sciencedaily.com/releases/2001/06/010605080118.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins