A conventional view of cystic fibrosis (CF) and its effects on the lungs is that it’s all about mucus. The inherited disease leads to an accumulation of mucus in the lungs, which appears to be connected with inflammation, susceptibility to infection and loss of lung capacity.
Immunologist Rabin Tirouvanziam has an alternative view, centered on neutrophils. They are a type of immune cell that is very numerous, yet often overlooked, he says.
Rabindra Tirouvanziam, PhD
A new paper, published in Journal of Leukocyte Biology, substantiates his ideas about cystic fibrosis and harnesses them for future diagnostic and therapeutic advances. Tirouvanziam is an assistant professor of pediatrics at Emory University School of Medicine and Emory Children’s Center. He and his colleagues have developed a system for studying neutrophil behavior in a specialized culture, a model of a cell layer in the lung.
Neutrophils behave differently in the diseased lung environment, compared with when they are in the blood. The culture system makes the neutrophils pass through a layer of lung cells, under the influence of lung fluids obtained from CF patients. The culture system opens up the opportunity of testing fluids from patients to mark disease progression, as well as drug discovery: looking for compounds that could deprogram the neutrophils. Read more
Low doses of the anti-cancer drug imatinib can spur the bone marrow to produce more innate immune cells to fight against bacterial infections, Emory and Winship Cancer Institute researchers have found.
The results were published this week in the journalÂ PLOS Pathogens.
The findings suggest imatinib, known commercially as Gleevec, or related drugs could help doctors treat a wide variety of infections, including those that are resistant to antibiotics, or in patients who have weakened immune systems. The research was performed in mice and on human bone marrow cellsÂ in vitro, but provides information on how to dose imatinib for new clinical applications.
â€œWe think that low doses of imatinib are mimicking â€˜emergency hematopoiesis,â€™ a normal early response to infection,â€ says senior author Daniel Kalman, PhD, associate professor of pathology and laboratory medicine at Emory University School of Medicine.
Imatinib, is an example of a â€œtargeted therapyâ€ against certain types of cancer. It blocks tyrosine kinase enzymes, which are dysregulated in cancers such as chronic myelogenous leukemia and gastrointestinal stromal tumors.
Imatinib also inhibits normal forms of these enzymes that are found in healthy cells. Several pathogens â€“ both bacteria and viruses â€“ exploit these enzymes as they transit into, through, or out of human cells. Researchers have previously found that imatinib or related drugs can inhibit infection of cells by pathogens that are very different from each other, includingÂ tuberculosis bacteriaÂ andÂ Ebola virus. Read more