Allergic Inflammation and Asthma Possibly linked to Pseudomonas Bacteria
Could some cases of asthma actually be caused by an allergic reaction to a common environmental bacteria? New research findings published in the Journal of Leukocyte Biology suggests that this is a possibility. In a research report appearing in the February 2012 print issue, researchers show a link between common environmental bacteria and airway inflammation. Specifically, their research suggests that some strains of Pseudomonas aeruginosa cause white blood cells to produce very high levels of histamine, which in turn leads to inflammation, a hallmark symptom of asthma.
In this five minute interview with Dr. George Caughey, M.D. Chief, Pulmonary/Critical Care/Sleep Medicine Section San Francisco VA Medical Center and Professor of Medicine at University of California, San Francisco (UCSF) School of Medicine we discuss the key studies findings, potential treatment options and laboratory test for Pseudomonas Bacteria.
“We hope that these findings in mice will encourage human-focused research regarding bacterial stimulation of histamine production by white blood cells, like neutrophils, that are not traditionally associated with allergic inflammation,” said Dr. George Caughey, M.D., a researcher involved in the work. “Such research could improve our understanding of inflammation in bacterial infections, and help us to craft therapies for relief of inflammation and its consequences for short and long-term health,” he noted. To make this discovery, scientists studied the effect of two strains of pseudomonas bacteria on isolated mouse white blood cells tasked with killing bacteria, called neutrophils.
To make this discovery, scientists studied the effect of two strains of pseudomonas bacteria on isolated mouse white blood cells tasked with killing bacteria, called neutrophils. Results showed that one strain killed the neutrophils, but the second strain produced substances that caused the neutrophils to increase their production of histamine significantly. To see if their discovery was applicable outside of the test tube, the histamine-stimulating strain was then used to infect mice to produce bronchitis and pneumonia. These mice experienced a significant increase of histamine in their airways and lungs. Additional work showed that the bacteria persuade neutrophils to produce histamine by causing them to make much more of the key enzyme in histamine synthesis (histidine decarboxylase) than neutrophils would otherwise do in the unstimulated state.
“Despite advances in diagnosing and treating the symptoms of asthma and allergy, our understanding of the underlying initiating events remains elusive,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. “This report helps shed light on how an ‘everyday organism’ might trigger asthma and allergy from an immune cell type not normally thought to be involved in allergic disease.”
About the Journal of Leukocyte Biology
The Journal of Leukocyte Biology (http://www.jleukbio.org) publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.
About George Caughey, M.D.
Dr. Caughey received an M.D. from Stanford. After Medicine and Pulmonary subspecialty training at Pennsylvania Hospital and UCSF, he trained in lung research at UCSF’s Cardiovascular Research Institute and at Genentech, joining UCSF’s pulmonary faculty in 1986. He occupies the Julius and Lillian Nadel Endowed Chair and is Chief of the Pulmonary and Critical Care Medicine Section at the San Francisco VA Medical Center. Major activities include laboratory-based research, teaching, inpatient and outpatient clinical consulting, and serving on editorial, administrative, and advisory committees.
Extracellular proteases influence the pathology of lung diseases. The lab is interested in the roles of known and novel proteases in normal and diseased lung, emphasizing roles in scarring, ion transport, and anti-bacterial defense. The lab’s traditional focus is on peptidases secreted by mast cells, which are resident inflammatory cells especially abundant in human lung. The lab characterized several of the major secreted mast cell serine proteases. Achievements include the first cloning of a tryptase and discovery of new functions of these enzymes as peptidases, secretagogues and modulators of muscle tone. These investigations encouraged pharmaceutical development of tryptase inhibitors. The lab characterized the multi-gene human tryptase locus, discovering novel genes encoding membrane-anchored (gamma) and truncated (delta) tryptases, as well as major polymorphisms and population-skewed inheritance of deficiency alleles like alpha and frame-shifted beta. A current thrust of research concerns clinical consequences of human variations in inheritance of mast cell tryptase genes.