Breaking News
December 19, 2018 - New $1.6 million NIH grant supports study on a gene vital to circadian rhythms
December 19, 2018 - Racial Disparities Seen Among Teens Undergoing Flu Vaccination
December 19, 2018 - To resolve inflammation, location matters
December 19, 2018 - Research identifies new therapeutic target for cancer treatment and tissue regeneration
December 19, 2018 - Energy costs, social isolation contribute to health risk of older adults in extreme weather
December 19, 2018 - Potential combination therapy against rare disease of the bone marrow could improve treatment
December 19, 2018 - Researchers aim to improve cognition, reverse weight gain in schizophrenia
December 19, 2018 - UC San Diego Health offers new DRG stimulation device for phantom limb pain
December 19, 2018 - Study examines relationship between growth restriction and risk of childhood mortality
December 19, 2018 - New study provides insights on increased risk of suicide in young patients visiting ED
December 19, 2018 - AHA: Thyroid Problems Linked to Worsening Heart Failure
December 19, 2018 - World-first coeliac disease vaccine enters Phase 2 trials
December 19, 2018 - RNA sequencing offers novel insights into the microbiome
December 19, 2018 - A promising, effective vaccine for common respiratory disease
December 19, 2018 - Protein may slow progression of emphysema, study finds
December 19, 2018 - Studying atrial fibrillation — and exploring new frontiers in precision health
December 19, 2018 - A New Way To Get College Students Through A Psychiatric Crisis — And Back To School
December 19, 2018 - Optum, UnitedHealthcare take action to help people affected by North Carolina winter storms
December 18, 2018 - Weight change in middle-aged, elderly Chinese Singaporeans related to increased risk of death
December 18, 2018 - Immune cells sacrifice themselves to protect us from invading bacteria
December 18, 2018 - Watching brain cells fire, with a twist of gravitational waves
December 18, 2018 - 2018 in Review
December 18, 2018 - Getting the Most Out of the CLARITY Technique
December 18, 2018 - NVF shoes provide a viable option for track and road racing
December 18, 2018 - CRISPR may restore effectiveness of chemotherapies used to treat lung cancer
December 18, 2018 - New app accurately measures and charts progression of skin wounds
December 18, 2018 - Persistent Discrimination ID’d Among Physician Mothers
December 18, 2018 - Cellphone technology developed to detect HIV
December 18, 2018 - A Stanford doctor hits the field with the 49ers — as their airway management physician
December 18, 2018 - The Rise of Anxiety Baking
December 18, 2018 - Just one night of sleep deprivation increases the urge to eat
December 18, 2018 - Study reveals mechanism behind failed remyelination in MS
December 18, 2018 - New genetic testing method increases the precision of biomarker analysis
December 18, 2018 - Simple technique to effectively treat underdiagnosed cause of debilitating chest pain
December 18, 2018 - Barbershop-based medical intervention can successfully lower blood pressure, new data shows
December 18, 2018 - Food labels have caused changes in consumers’ intake and industry’s use of key additives
December 18, 2018 - Sickest children could benefit from split liver transplants
December 18, 2018 - Scientists create patient-specific model to identify most effective treatment for appendix cancer
December 18, 2018 - ‘Little Foot’ endocast reveals a small brain combining ape-like and human-like features
December 18, 2018 - New therapy for childhood blindness shows ‘very promising’ results
December 18, 2018 - Researchers discover promising new compound against Buruli ulcer
December 18, 2018 - Study finds significant use of traditional, complementary and alternative medicines in Sub-Saharan Africa
December 18, 2018 - California Farm Implicated in Outbreak of E. coli Tied to Romaine Lettuce
December 18, 2018 - Mobile health has power to transform HIV/AIDS nursing
December 18, 2018 - Celiac Vaccine in Clinical Trials at Columbia
December 18, 2018 - Research into mental health first aid prompts practical guidance and resources for workplace
December 18, 2018 - Researcher conducts study to investigate peripheral blood markers of Alzheimer’s disease
December 18, 2018 - Researchers identify link between mucus in the small airways and pulmonary fibrosis
December 18, 2018 - EU Commission’s Health Policy Platform to host EKHA program on transplantation
December 18, 2018 - Survivors of childhood Hodgkin lymphoma have high risk of developing solid tumors
December 18, 2018 - Small changes to cafeteria design can get kids to eat healthier, new assessment tool finds
December 18, 2018 - From Machines to Cyclic Compounds
December 18, 2018 - New study reveals best assessment tools to establish delirium severity
December 18, 2018 - Rice University scientists develop synthetic protein switches to control electron flow
December 18, 2018 - Home-based pulmonary function monitoring for teens with Duchenne muscular dystrophy
December 18, 2018 - Researchers identify potential target for new breast cancer treatments
December 18, 2018 - National Biofilms Innovation Centre award grant to Neem Biotech for novel anti-biofilm drug development
December 18, 2018 - Artificial intelligence and the future of medicine
December 18, 2018 - Montana State doctoral student receives grant for her work to improve neuroscience tool
December 18, 2018 - Early postpartum initiation of opioids associated with persistent use
December 18, 2018 - Russian scientists identify molecular ‘switch’ that could be target for treatment of allergic asthma
December 18, 2018 - Surgeons make more mistakes in the operating room during stressful moments, shows study
December 18, 2018 - Immune cells explode themselves to inform about the danger of invading bacteria
December 18, 2018 - Malnutrition in children with Crohn’s disease linked with increased risk of surgical complications
December 18, 2018 - FDA Approves Motegrity (prucalopride) for Adults with Chronic Idiopathic Constipation (CIC)
December 18, 2018 - The long and short of CDK12
December 18, 2018 - Hologic’s Cynosure division introduces TempSure Surgical RF technology in North America
December 18, 2018 - CMR Surgical partners with Nicholson Center to launch U.S.-based training program for Versius
December 18, 2018 - Findings reinforce guidelines for cautious use of antipsychotics in younger populations
December 18, 2018 - Study finds new strains of hepatitis C virus in sub-Saharan Africa
December 18, 2018 - New battery-free, implantable device aids weight loss
December 18, 2018 - Parental alcohol use disorder associated with offspring marital outcomes
December 18, 2018 - Novel Breast Imaging Technique Might Cut Unnecessary Biopsies
December 18, 2018 - What can a snowflake teach us about how cancer spreads in the body?
December 18, 2018 - Management of nausea and vomiting in pregnancy costs the NHS more than previously thought
December 18, 2018 - Green leafy vegetables may reduce risk of developing liver steatosis
December 18, 2018 - Veganism linked to nutrient deficiencies and malnutrition if not planned correctly
December 18, 2018 - Coming Soon: A Tiny Robot You Swallow to Help You Stay Healthy
December 18, 2018 - Modified malaria drug proven effective at inhibiting Ebola
December 18, 2018 - Study finds epigenetic differences in the brains of individuals with schizophrenia
Researchers reveal new tactic to fight antibiotic-resistant pneumonia

Researchers reveal new tactic to fight antibiotic-resistant pneumonia

image_pdfDownload PDFimage_print

Antibiotic resistance is a growing threat in bacterial pneumonia. While immune-stimulating treatments can help the body kill the bacteria, they can also cause inflammation that damages and weakens lung tissue. Researchers at Boston Children’s Hospital now describe an approach that offers the best of both worlds: enhanced bacterial killing with reduced lung damage.

Their findings were published April 4th in Science Translational Medicine.

When the immune system sees a bacterial infection, it triggers an influx of cells known as neutrophils at the infection site. Neutrophils can kill the bacteria, but they also cause harm by releasing inflammatory compounds that damage the lung’s air sacs.

“The question is, when we have pneumonia, do we want to enhance neutrophil function or suppress it? It’s very tricky,” says Hongbo (Robert) Luo, PhD, a researcher in the Department of Laboratory Medicine at Boston Children’s Hospital and senior investigator on the study.

Fewer but stronger neutrophils

Luo’s lab has long been studying an enzyme called IP6K, and recently showed that it inhibits signaling by another molecule in neutrophils called PIP3. When IP6K is inhibited in a mouse model, PIP3 becomes elevated and neutrophils become more active, killing more bacteria and living longer – “like ‘super’ neutrophils,” says Luo.

Luo’s team, with collaborators at the Chinese Academy of Medical Sciences and Peking Union Medical College in China, decided to further investigate IP6K1’s role in neutrophil function in a mouse model of bacterial pneumonia. When the team deleted the IP6K1 gene in the mice, they saw enhanced bacterial killing by neutrophils, which more actively engulfed bacteria and killed them with toxic compounds.

But the researchers also saw reduced neutrophil accumulation in the lungs’ air spaces and reduced lung damage. “This was a surprise,” says Luo. “The exciting thing is that bacterial killing is high, and tissue damage is low.”

When the researchers used an IP6K inhibitor drug called TNP instead of genetic manipulation, results were the same.

The role of platelets

Why was there less neutrophil accumulation? The team found that the effect was occurring through blood platelets, which produce a chemical regulator known as polyphosphate that make neutrophils more active and apt to migrate.

“When we inhibit IP6K, platelets make less polyphosphate, reducing neutrophil recruitment,” explains Luo. “But when the neutrophils get there, they kill bacteria more. We have a treatment that can enhance neutrophils’ bacterial killing activity, but their recruitment is controlled, so we have better outcomes.”

Luo cautions that TNP has never been tested as a potential drug in humans. But he thinks the study findings may have implications not just for bacterial pneumonia, but for other infections that involve neutrophils.

In addition, Boston Children’s Transfusion Medicine group, where Luo’s lab is based, is interested in pursuing IP6K inhibition in cancer patients, who often have severely reduced neutrophil counts that put them at high risk for infection.

“We could try transfusing neutrophils, treated with TNP to enhance neutrophil function, but leaving platelets untreated so that neutrophil recruitment wouldn’t be inhibited,” Luo says.

Source:

http://www.childrenshospital.org/

Tagged with:

About author

Related Articles