Seven out of ten top leading causes of mortality in the developed world (from atherosclerosis and heart disease to diabetes and cancer) share a common pathology: chronic inflammation. Diagnosis is often made when the damage to critical organs is already significant and irreversible because none of the existing inflammation markers is appropriate for early detection of chronic inflammation conditions. To change the status-quo, we will rely on emerging knowledge proposing new roles for neutrophils - the typical innate immune cell to protect us against microbes - in chronic inflammation. Observations in transgenic animals showed that some neutrophils are capable of reversing migration from tissues to circulation after responding to a sterile injury. Recently, we have been able to replicate the reversed-migration patterns in a novel in vitro device. The major goal of this proposal is to continue improving the design of these devices, to identify and characterize the modulators of reversed-migration in vitro, and to design more sophisticated technologies that can separate the neutrophils undergoing reversed migration, for subsequent genomic and proteomic analysis. These tools would enable us to characterize the reversely-migrated neutrophils in detail and to identify specific markers that could differentiate the reversely-migrated neutrophils from naive neutrophils in blood samples from patients with chronic inflammation. If successful, our research could lead to new methods for monitoring chronic inflammation, could enable early diagnosis, allow sufficient time to adopt lifestyle changes, assist early treatments, and could have major implications for reducing morbidity and mortality associated with chronic inflammation diseases.
Chronic inflammation is the pathology responsible for seven of the top ten leading causes of mortality in the developed world, from atherosclerosis and heart disease to diabetes and cancer. Neutrophils, the white blood cells involved in protecting us against microbes, have been recently shown to participate in the initiation, tissue damage, and persistence of chronic inflammation. To better understand this pathology, we propose to develop novel microfluidic tools that will enable the study in vitro of the newly discovered migration patterns that return neutrophils from tissues into circulation, which could ultimately become a maker for ongoing chronic inflammation processes.
