Scientists find new evidence about how to prevent worsening pneumonia

September 5, 2017
Sodium channels in the cells that line the tiny capillaries in our lungs play an important role in keeping those capillaries from leaking and potentially worsening conditions like pneumonia, scientists report. from left, Drs. Supriya Sridhar, Maritza J. Romero-Lucas, Rudolf Lucas and Istvan Czikora. Credit: Phil Jones, Senior Photographer Augusta University

Sodium channels in the cells that line the tiny capillaries in our lungs play an important role in keeping those capillaries from leaking and potentially worsening conditions like pneumonia, scientists report.

The TIP peptide, a synthetic version of the tip of the cancer-killing immune molecule tumor necrosis factor, appears to strengthen that barrier function, according to the study in the journal Frontiers in Immunology.

TIP's protection works even in the face of pneumolysin, a released in large volume in response to antibiotic treatment to kill pneumonia-causing bacterium. The toxin can create tiny holes in the natural barriers of both capillaries as well as air sacs in the lungs. The result can be a second and potentially deadly wave of fluid accumulation in the lungs in about 20 percent of the sickest pneumonia patients.

"We showed that these channels are present in human capillary and that these channels play a really important role in protecting us from pneumolysin," says Dr. Rudolf Lucas, vascular biologist at the Vascular Biology Center at the Medical College of Georgia at Augusta University and the study's corresponding author.

"We also provided more evidence that targeting these channels with the TIP peptide or something similar is a solid strategy for reducing dangerous fluid volume in your lungs," says Lucas. The studies were conducted in the endothelial cells that line human capillaries, known to form a tight barrier for the blood vessels.

Tiny capillaries and air sacs, or alveoli, in the lungs have thin walls and close proximity which enable the capillaries to pick up oxygen from the air sacs and carry it forward to the rest of the body. The toxin makes the usually tight lining of the capillaries leaky so blood and other fluid can get into the lung tissue, even into the air sacs. The lungs can become overwhelmed with fluid, and the body doesn't get the oxygen it needs.

Similarly, sodium transport channels in the air sacs are negatively impacted by the toxin.

The function of the epithelial sodium , or ENaC, which helps move fluid out of air sacs normally, is even more in demand in the face of pneumonia, but the toxin impairs its ability in both the air sacs and capillaries, the scientists have now shown.

The scientific team working through the complex interchange found that in the capillaries of the lung, an important subunit of ENaC - called ENaC-alpha - is important as well to strengthening the barrier function of the blood vessels. They then showed that the TIP peptide, which they developed and know binds to ENaC-alpha, significantly strengthened the barrier in human endothelial cells exposed to the toxin.

They also found at work in the barrier function, a hybrid of ENaC-alpha and the acid sensing ion channel, known for its pain-mediating contributions in the brain. A troubled lung also becomes acidic, which can activate this acid sensing ion channel. They found their TIP peptide also activates the unique hybrid it makes with ENaC-alpha.

"Patients are being treated with antibiotics, which they need to kill the bugs," Lucas notes. The problem is, once you kill the bugs in large quantities, they can release huge amounts of this toxin into the lungs and these toxins make holes, literally holes in membranes of every cell containing cholesterol."

Pulmonologists and other critical care specialists recognize the subsequent problems that can result from high levels of the pneumolysin toxin, but currently don't have a direct solution, Lucas says. Ventilator support can help push oxygen through the fluid-filled sacs, but carries the risk of letting even more bugs into the lungs as well as physical damage to lung tissue.

There also is currently no way to identify ahead of time which patients will experience this second wave, Lucas says. Children are particularly vulnerable because their immune systems also mount a vigorous attack against the invading bacterium and so even more toxin results from the dying bug. Pneumonia is a top killer of children under age five across the world, according to the World Health Organization, along with preterm birth complications, birth asphyxia, diarrhea, malaria and malnutrition.

The TIP peptide is attracted to the sugar coating at the mouth of the sodium channel.

Lucas led a team of scientists who reported in 2014 that the TIP peptide worked like a doorstop to keep inside open in animal models.

Results of a clinical study led by the University of Vienna, also published this year in the journal Critical Care, showed that patients with more severe pulmonary edema - fluid in their lungs - who required a ventilator to support their breathing were able to better clear fluid from their lungs following inhaled treatment with the Tip peptide. Others did not appear to benefit.

Explore further: Cancer fighter can help battle pneumonia

Related Stories

Cancer fighter can help battle pneumonia

August 5, 2014
The tip of an immune molecule known for its skill at fighting cancer may also help patients survive pneumonia, scientists report.

Stimulation of brain hormone action may improve pneumonia survival

January 31, 2012
An international research team may have found a way to block a second wave of death that can result from pneumonia treatment.

New proteins to clear the airways in cystic fibrosis and COPD

July 13, 2012
University of North Carolina scientists have uncovered a new strategy that may one day help people with cystic fibrosis and chronic obstructive pulmonary disorder better clear the thick and sticky mucus that clogs their lungs ...

Caffeine reduces oxidative stress, improves oxygen-induced lung injury

March 9, 2017
A new study finds that caffeine may protect the lungs from damage caused by prolonged oxygen therapy, such as oxygen supplementation given to premature babies. The article is the first of its kind to study the positive effects ...

Recommended for you

Gene immunotherapy protects against multiple sclerosis in mice

September 21, 2017
A potent and long-lasting gene immunotherapy approach prevents and reverses symptoms of multiple sclerosis in mice, according to a study published September 21st in the journal Molecular Therapy. Multiple sclerosis is an ...

New academic study reveals true extent of the link between hard water and eczema

September 21, 2017
Hard water damages our protective skin barrier and could contribute to the development of eczema, a new study has shown.

Exposure to pet and pest allergens during infancy linked to reduced asthma risk

September 19, 2017
Children exposed to high indoor levels of pet or pest allergens during infancy have a lower risk of developing asthma by 7 years of age, new research supported by the National Institutes of Health reveals. The findings, published ...

Cholesterol-like molecules switch off the engine in cancer-targeting 'Natural Killer' cells

September 18, 2017
Scientists have just discovered how the engine that powers cancer-killing cells functions. Crucially, their research also highlights how that engine is fuelled and that cholesterol-like molecules, called oxysterols, act as ...

MicroRNA helps cancer evade immune system

September 18, 2017
The immune system automatically destroys dysfunctional cells such as cancer cells, but cancerous tumors often survive nonetheless. A new study by Salk scientists shows one method by which fast-growing tumors evade anti-tumor ...

'Exciting' discovery on path to develop new type of vaccine to treat global viruses

September 15, 2017
Scientists at the University of Southampton have made a significant discovery in efforts to develop a vaccine against Zika, dengue and Hepatitis C viruses that affect millions of people around the world.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.