Lipid-Derived Mediators are Pivotal to Leukocyte and Lung Cell Responses in Sepsis and ARDS

Abstract

Acute inflammation in the lung is essential for host defense against pathogens and other injuries but chronic or excessive inflammation can contribute to several common respiratory diseases. In health, the inflammatory response is controlled by several cellular and molecular mechanisms. In addition to anti-inflammatory processes, there are non-phlogistic pro-resolving mechanisms that are engaged to promote the resolution of inflammation and a return to homeostasis. Defects in the production or actions of specialized pro-resolving mediators are associated with diseases characterized by excess or chronic inflammation. In this article, we review cellular and biochemical mechanisms for specialized pro-resolving mediators in health and in sepsis and the acute respiratory distress syndrome as examples of unrestrained inflammatory responses that result in life-threatening pathology. We are honored to contribute to this special edition of the Journal to help celebrate Professor Viswanathan Natarajan's contributions to our understanding of lipid-derived mediators and metabolism in lung cell responses to inflammatory, infectious, or mechanical insults; his foundational discoveries in cell biochemistry and biophysics are continuing to catalyze further advances by the field to uncover the mechanistic underpinnings of important human diseases.

Keywords: Inflammation; Neutrophils; Phospholipase D; Presqualene diphosphate; Resolution; Specialized pro-resolving mediators.