Featured Research

from universities, journals, and other organizations

New Cell-based Targets For Treating Autoimmune Inflammatory Diseases

Date:
September 4, 2006
Source:
John Wiley & Sons, Inc.
Summary:
A new study indicates the critical role of platelet function in this dire form of autoimmune kidney disease, crescentic glomerulonenephritis (CGN).

Patients with systemic autoimmune diseases such as lupus and rheumatoid arthritis (RA) often suffer loss of kidney function. When marked by a crescent formation in the glomerulus -- a tiny ball comprised of capillary blood vessels integral to forming urine -- kidney failure tends to be rapidly progressive, irreversible, and fatal. Little is known about the mechanism behind this crescent or its relationship to immune-mediated inflammation.

Related Articles


To gain understanding, a team of researchers in Japan began by analyzing a spontaneous mutant strain of EOD mice. Their study, published in the September 2006 issue of Arthritis & Rheumatism, indicates the critical role of platelet function in this dire form of autoimmune kidney disease, crescentic glomerulonenephritis (CGN). It also sheds light on the involvement of Cno protein, a member of a large protein complex called biogenesis of lysosome-related organelle complex 1 (BLOC-1), in the development of an autoimmune disease.

Researchers isolated this mutant strain of mice from the autoimmune-prone strain EOD, which stably develops fatal CGN. Then, using blood samples, they thoroughly assessed blood cell count, immune function, platelet function, and properties of various cell types and genes in these mice, searching for clues to their marked improvement in CGN and ability to survive about twice as long as wild-type EOD mice. Among the surprising findings in the mutant mice was an ability to alter platelet functions. While wild-type EOD mice displayed massive accumulations of platelets in the glomerulus, the mutant mice did not, but they were more prone to bleeding. Further investigation revealed a mutation in the cappuccino gene, which encodes the Cno protein. Mutant platelets also showed abnormally low aggregation in response to collagen and abnormally low rates of serotonin storage.

These findings suggest links between the gene mutation, loss of Cno protein expression, defect in platelet function, and the regression of crescent formation in the glomerulus. What's more, these links are related to BLOC-1, which controls lysosomes, tiny organelles that contain digestive enzymes critical to maintaining healthy cell function.

"The profound role of BLOC-1 appears to be platelet-specific among immuno-inflammatory cell types," notes the study's lead author, Dr. Masao Ono from the Tohoku University Graduate School of Medicine. "BLOC-1 is a possible therapeutic target for suppression of platelet functions without compromising physiologic immune responses."

In another promising new study, using rats and gene-modified mice, researchers in Turku, Finland, uncovered a new type of adhesion molecule highly expressed on vessels of inflamed human synovial tissue. This molecule, AOC3 (amine oxidase, copper-containing 3; also known as vascular adhesion protein 1), works to spur inflammation by thwarting the infiltration of leukocytes, vital white blood cells, into rheumatoid joints. In an editorial describing the discovery and function of this adhesive enzyme, Dr. Beat A. Imhof of the University of Geneva School of Medicine and University Hospital, Geneva, Switzerland, indicates the potential therapeutic value for rheumatoid arthritis patients. "Antiadhesive therapies based on the use of small molecule inhibitors certainly represent an economically interesting alternative to expensive biologic treatments, such as humanized anti-adhesion molecule antibodies, which are currently being developed for the treatment of inflammatory diseases," Dr. Imhof notes.

Article: "Cappuccino Mutation in an Autoimmune-Prone Strain of Mice Suggests a Role of Platelet Function in the Progression of Immune Complex Crescentic Glomerulonephritis," Minako Yoshida, Kan Saiga, Takaaki Hato, Shoko Iwaki, Toshiyuki Niiya, Norimasa Arita, Hiroaki Komori, Takahito Tsubaki, Hiroshi Furukawa, Miho Terada, Kazutaka Maeyama, Kyuichi Nemoto, Masato Nose, and Masao Ono, Arthritis & Rheumatism, September 2006; (DOI: 10.1002/art.22059).

Article: "Vascular Amine Oxidases Are Needed for Leukocyte Extravasation Into Inflamed Joints In Vivo," Fumiko Marttila-Ichara, David J. Smith, Craig Stolen, Gennady G. Yegutkin, Kati Elima, Nathalie Mercier, Riku Kiviranta, Marjo Pihlavisto, Sakari Alaranta, Ulla Pentikäinen, Olli Pentikäinen, Ferenc Fölüp, Sirpa Jalkanen, and Marko Salmi, Arthritis & Rheumatism, September 2006; (DOI: 10.1002/art.22061).

Editorial: "Leukocyte Migration to Rheumatoid Joints: Enzymes Take Over," Gaby Palmer, Cem Gabay, and Beat A. Imhof, Arthritis & Rheumatism, September 2006; (DOI: 10.1002/art.22062).


Story Source:

The above story is based on materials provided by John Wiley & Sons, Inc.. Note: Materials may be edited for content and length.


Cite This Page:

John Wiley & Sons, Inc.. "New Cell-based Targets For Treating Autoimmune Inflammatory Diseases." ScienceDaily. ScienceDaily, 4 September 2006. <www.sciencedaily.com/releases/2006/08/060831084442.htm>.
John Wiley & Sons, Inc.. (2006, September 4). New Cell-based Targets For Treating Autoimmune Inflammatory Diseases. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2006/08/060831084442.htm
John Wiley & Sons, Inc.. "New Cell-based Targets For Treating Autoimmune Inflammatory Diseases." ScienceDaily. www.sciencedaily.com/releases/2006/08/060831084442.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) — It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) — More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) — In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) — The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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