Featured Research

from universities, journals, and other organizations

Scientists Discover What Drives The Development Of A Fatal Form Of Malaria

Date:
August 19, 2008
Source:
Johns Hopkins Medical Institutions
Summary:
In a study described in Cell Host and Microbe, researchers reveal that when red blood cells are infected with the malaria parasite, they activate platelets to secrete the PF4 protein, which triggers the immune system to inflame blood vessels and obstruct capillaries in the brain; both are hallmarks of cerebral malaria.

Platelets – those tiny, unassuming cells that cause blood to clot and scabs to form when you cut yourself – play an important early role in promoting cerebral malaria, an often lethal complication that occurs mostly in children. Affecting as many as half a billion people in tropical and subtropical regions, malaria is one of the oldest recorded diseases and the parasite responsible for it, Plasmodium, among the most studied pathogens of all time.

Still, cerebral malaria, which results from a combination of blood vessel and immune system dysfunction, is not well understood.

In a study described in the August 14 issue of Cell Host and Microbe, Johns Hopkins researchers reveal that when red blood cells are infected with the malaria parasite, they activate platelets to secrete the PF4 protein, which triggers the immune system to inflame blood vessels and obstruct capillaries in the brain; both are hallmarks of cerebral malaria.

In their experiments, the Hopkins team first infected human red blood cells in culture with the malaria parasite and found that this did, indeed, induce platelet activation.

The researchers then infected separate sets of live mice with the malaria parasite: one set treated so that it lacked platelets altogether and two others treated with aspirin or Plavix, platelet inhibitors that prevent the release of PF4.

The survival rate of mice without platelets as well as those treated with inhibitors was improved over that of the mice left alone, but only when the treatment began very soon after infection. When researchers started treating mice with platelet inhibitors one day after infecting them, those mice survived more often than control mice. However, when researchers waited until after three days to treat infected mice with platelet inhibitors, that group did no better in terms of survival.

"Cerebral malaria is lethal 20 percent of the time in the best of hands, and here we've shown that something as simple as aspirin, because of its affect on platelets, might be able to improve the outcomes of those who contract this deadly form of the disease," says David Sullivan M.D., an associate professor of molecular microbiology and immunology in the Johns Hopkins University Bloomberg School of Public Health.

To make the specific connection between PF4 and malaria, the scientists compared the responses to malaria infection by so-called "wild type" normal mice and mice genetically engineered to lack pF4. They found that the amount of parasite in the blood was the same in both sets of mice. The notable difference was in the animals' immune responses to that same parasite burden. More than 60 percent of the mice lacking PF4 were still alive after day 10, while only 30 percent of the mice with PF4 survived that long.

"The take-home lesson is that platelets, by releasing PF4, are playing an early role in the wind-up phase of cerebral malaria," says Craig Morrell, DVM, Ph.D., an assistant professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine. "Our mouse studies show that timing is critical; with the mice, we know when we infected them and controlled when we treated them. A big challenge in translating this to humans is that people don't know when they get infected.

"Platelets don't get any respect, but they're the second most abundant cell in the blood after red blood cells and packed full of factors that rally the immune system to action. By taking what we know about platelets and their activation and applying it to malaria, we have found a driver of cerebral malaria."

The research was funded by the National Institutes of Health and supported by the Johns Hopkins Malaria Research Institute.

Authors on the paper are Kalyan Srivastava, Ian A. Cockburn, Anne Marie Swaim, Laura E. Thompson, Abhai Tripathi, Craig A. Fletcher, Erin M. Shirk, Henry Sun, Karen Fox-Talbot, David Sullivan, Fidel Zavala, and Morrell, all of Hopkins: also, M. Anna Kowalska of The Children's Hospital of Philadelphia, Pa.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "Scientists Discover What Drives The Development Of A Fatal Form Of Malaria." ScienceDaily. ScienceDaily, 19 August 2008. <www.sciencedaily.com/releases/2008/08/080818184255.htm>.
Johns Hopkins Medical Institutions. (2008, August 19). Scientists Discover What Drives The Development Of A Fatal Form Of Malaria. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2008/08/080818184255.htm
Johns Hopkins Medical Institutions. "Scientists Discover What Drives The Development Of A Fatal Form Of Malaria." ScienceDaily. www.sciencedaily.com/releases/2008/08/080818184255.htm (accessed August 28, 2014).

Share This




More Plants & Animals News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Super Healthful Fruits and Vegetables: Which Are Best?

Super Healthful Fruits and Vegetables: Which Are Best?

Ivanhoe (Aug. 27, 2014) We all know that it is important to eat our fruits and vegetables but do you know which ones are the best for you? Video provided by Ivanhoe
Powered by NewsLook.com
Bad Memories Turn Good In Weird Mouse Brain Study

Bad Memories Turn Good In Weird Mouse Brain Study

Newsy (Aug. 27, 2014) MIT researchers were able to change whether bad memories in mice made them anxious by flicking an emotional switch in the brain. Video provided by Newsy
Powered by NewsLook.com
Do Couples Who Smoke Weed Together Stay Together?

Do Couples Who Smoke Weed Together Stay Together?

Newsy (Aug. 27, 2014) A study out of University at Buffalo claims couples who smoke marijuana are less likely to experience intimate partner violence. Video provided by Newsy
Powered by NewsLook.com
Panda Might Have Faked Pregnancy To Get Special Treatment

Panda Might Have Faked Pregnancy To Get Special Treatment

Newsy (Aug. 27, 2014) A panda in China showed pregnancy symptoms that disappeared after two months of observation. One theory: Her pseudopregnancy was a ploy for perks. 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