Your health can’t wait. Learn how we’re making our facilities safer and schedule your care now.
Children's Hospital is part of the UPMC family.
Be safe anytime, anywhere.
To find a pediatrician or pediatric specialist, please call 412-692-7337 or search our directory.
A resource for our network of referring physicians.
For more information about research, please call our main office at 412-692-6438.
Ranked #9 Nationally by U.S. News & World Report.
Children’s Hospital of Pittsburgh of UPMC and University of Pittsburgh School of Medicine researchers have uncovered a new mechanism governing the integrity of capillaries, the smallest branches of the circulatory system. The study is published in the current issue of the journal Cell Reports.
Capillaries are lined by endothelial cells, which can maintain a water-tight barrier to prevent leakage of fluid from the bloodstream into surrounding tissue. However, under certain conditions, these cells can be stimulated to induce a rapid but temporary increase in the leakiness of this barrier. This allows fluid and immune cells to exit the bloodstream and accumulate in tissue leading to a condition known as “edema,” a cornerstone of the body’s inflammatory response.
While this acute increase in permeability is important for normal inflammation, it can cause more harm than good if left unchecked. In a broad range of conditions, from acute hypersensitivity responses such as a bee sting reaction or asthma attack, to brain swelling in trauma patients, excessive capillary leakiness can become life threatening.
A lack of knowledge about how endothelial cells regulate permeability has resulted in current therapies being mostly supportive in nature, directed at overcoming the consequences of edema and inflammation. This study highlights the unexpected role for an enzyme, MALT1, in mediating endothelial permeability initiated by several key inflammatory stimuli.
To study the role of MALT1, researchers used a mouse model which mimicked a state of septic shock, a life-threatening inflammatory condition which can lead to excessive fluid accumulation in the lungs. Mice genetically deficient in MALT1 enzymatic activity were protected from this fluid accumulation, demonstrating the crucial role of MALT1 activation in increasing leakiness of the endothelial barrier.
“Armed with this new knowledge, we can now begin to think about how targeting MALT1 might be an effective strategy for curtailing excessive, acute capillary leakiness in a range of clinical scenarios”, said Linda McAllister-Lucas, M.D., Ph.D., chief, Division of Pediatric Hematology/Oncology at Children’s Hospital and a senior author on the study.
To that end, the research group is now focused on compounds that were used several decades ago in the field of psychiatry but only recently discovered to inhibit MALT1 effectively.
“It’s particularly exciting to contemplate how an old class of pharmaceuticals, the phenothiazines, might be quickly repurposed for use in an entirely new therapeutic arena; the treatment of acute edema,” said
Peter Lucas, M.D., Ph.D., associate professor of pathology and pediatrics at Pitt School of Medicine and the study’s co-senior author.
The authors consider their current work as a “proof-of-principle” that pharmacologic MALT1 inhibition might have therapeutic benefit in conditions associated with capillary leak such as sepsis, trauma or allergic/hypersensitivity reactions.
The work was supported primarily by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health (R01-HL082914).
Children's Hospital's main campus is located in the Lawrenceville neighborhood. Our main hospital address is:
UPMC Children’s Hospital of Pittsburgh
One Children’s Hospital Way
4401 Penn Ave.
Pittsburgh, PA 15224
In addition to the main hospital, Children's has many convenient locations in other neighborhoods throughout the greater Pittsburgh region.
With myCHP, you can request appointments, review test results, and more.
For questions about a hospital bill call:
To pay your bill online, please visit UPMC's online bill payment system.
Interested in giving to Children's Hospital? Support the hospital by making a donation online, joining our Heroes in Healing monthly donor program, or visiting our site to learn about the other ways you can give back.