Researchers at Mount Sinai School of Medicine have just developed an advanced imaging technique to capture the movement of the microdomains of leukocytes or white blood cells. Microdomains are restricted areas on the surface of the cells in which receptors and signaling molecules accumulate during cell activation. Using digital multi-channel videomicroscopy, researchers were able to view white blood cell subsets and their forming microdomains in the vascular system in real time. In the upcoming March issue of Nature Methods, the new research displays the migration and inner workings of white blood cells in the small veins and bone marrow of mice.
"Intravital micropscopy (IVM) has contributed enormously to the recent mechanistic advances in leukocyte trafficking," wrote Mount Sinai School of Medicine researchers lead author Elaine Y. Chiang, Andres Hidalgo, Jungshan Chang and Paul S. Frenette of the Department of Medicine’s Immunobiology Center and Black Family Stem Cell Institute in New York. "Multichannel digital fluorescence videomicropscopy vastly improves on prior intravital observations of leukocyte behavior in vivo by allowing the near-simultaneous observation of cell surface markers and microdomains."
Researchers explored various mouse models including that of Sickle Cell disease which is a common inherited blood disorder in the United States, affecting 72,000 Americans according to the National Institutes of Health (NIH). Sickle Cell disease is a blood disorder that affects hemoglobin, a protein inside red blood cells that help carry oxygen throughout the body. Abnormal hemoglobin polymerizes, and red blood cells become sickle-shaped. Sickle-shaped red blood cells then clog blood vessels by sticking to white blood cells and depriving the body of needed oxygen.
Using this new imaging method, red blood cells in a mouse model of Sickle Cell disease were shown to interact specifically with neutrophils, a subset of inflammatory white blood cells. "The ease and rapidity of this method, and the abilty to combine it with current genetic labeling techniques will greatly aid investigations to elucidate in vivo imflammatory cell behavior, and provide a powerful tool for the development of therapeutics for these diseases," according to Mount Sinai researchers.
"Sickle cell anemia was the first disease characterized at the molecular level but there is still no treatment for the acute vascular occlusions which are the hallmark of the disease," said Mount Sinai researcher Dr. Paul S. Frenette. "In vivo imaging provides a window inside the body that allows us to see exactly which blood cells and which molecular constituents participate in the vascular occlusions. Advances in molecular imaging will likely lead to new targets for the treatment that will improve the life of patients afflicted by this terrible illness."
Mount Sinai’s research was done in collaboration with the National Heart, Lung and Blood Institute (NHLBI) of the NIH.
About The Mount Sinai Hospital
The Mount Sinai Hospital is one of the nation’s oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care.
About Mount Sinai School of Medicine
Located in Manhattan, Mount Sinai School of Medicine is internationally recognized for ground-breaking clinical and basic-science research, and innovative approaches to medical education. Through the Mount Sinai Graduate School of Biological Sciences, Mount Sinai trains biomedical researchers with an emphasis on the rapid translation of discoveries of basic research into new techniques for fighting disease. One indication of Mount Sinai’s leadership in scientific investigation is its receipt during fiscal year 2005 of $174.1 million in research support from NIH. Mount Sinai School of Medicine also is known for unique educational programs such as the Humanities in Medicine program, which creates opportunities for liberal arts students to pursue medical school, and instructional innovations like The Morchand Center, the nation's largest program teaching students and physicians with "standardized patients" to become not only highly skilled, but compassionate caregivers. Long dedicated to improving its community, the School extends its boundaries to work with East Harlem and surrounding communities to provide access to health care and educational programs to at risk populations.
Journal
Nature Methods