Find a Doctor

G. Scott Worthen, MD

Physician-Scientist in Neonatology

Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

Our laboratory is interested in the mechanisms by which polymorphonuclear leukocytes (neutrophils) are attracted to, and potentially injure, the lung. The lung has a unique architecture and physiology that results in a large number of neutrophils within the lung microcirculation under even normal circumstances. Following an inflammatory response in the lung, neutrophils are further recruited from the bone marrow into the circulation, and thence are avidly retained within the lung. We are interested in mechanisms of recruitment during inflammation, as well as the feedback loops that control neutrophil number under both homeostatic and inflammatory conditions.

Neutrophil number in the circulation is regulated in a complex fashion that senses neutrophil accumulation at a sentinel site, which we believe is the gut. Chemokine CXCL5 secretion by the gut epithelium attracts neutrophils, which are then sensed by phagocytic cells that secrete a variety of cytokines. Recognition of neutrophils is accompanied by decreased secretion of IL-l and IL-23, cytokines which drive differentiation of IL-17-producing cells. IL-17 in tum, then induces production of G-CSF and other CXC chemokines, thus contributing to release of neutrophils from the bone marrow. Somewhat surprisingly, the gut microbiome is involved in establishing the "setpoint" for these cytokines, and hence the neutrophil number. This complex feedback system is deranged in mice deficient in CXCL5, or the receptor for CXC chemokines, CXCR2. It is also abnonnal in mice and humans deficient in CD18.

Within Neonatology, we are particularly interested in the period during which the neonate acquires its repertoire of microbes in the gut and other sites. We are interested in the idea that this process sets in motion this feedback mechanism, and thus may be critically important for the adaptation of neonates to a world containing microbes.

« Back to Previous Page
  • Print
  • Share

Contact Us