Plasma gelsolin improves host defense

Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function

Zhiping Yang , Terry Ting-Yu Chiou , Thomas P. Stossel , Lester Kobzik

American Journal of Physiology - Lung Cellular and Molecular Physiology Published 1 July 2015 Vol. 309 no. 1, L11-L16 DOI: 10.1152/ajplung.00094.2015 

Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide, and bacterial pneumonia occurring post-influenza infection is a devastating complication.  With the growing problem of antibiotic-resistant bacterial species, it is imperative for scientists to investigate ways to enhance the body’s own immune defense against potentially pathogenic microorganisms.  In terms of respiratory infections, the alveolar macrophage within the lung is the sentinel phagocyte responsible for patrolling airspaces and clearing pathogens.  In this issue of AJP Lung, Yang et al. describe the ability of a protein normally found in human blood called plasma gelsolin to enhance the ability of alveolar macrophages to kill ingested pathogens.  Plasma gelsolin has previously been shown to have beneficial functions for limiting inflammatory reactions, and it has been known that levels of plasma gelsolin can be depleted during acute pneumonia in humans, but no previous studies had directly shown evidence that it could enhance bacterial killing functions.  This interesting study demonstrated plasma gelsolin could increase the rate at which macrophages ingest bacteria as well as increase the efficiency of killing the bacteria once engulfed.  Importantly, these effects were via direct actions on the macrophages and not caused by simple opsonization of the bacteria.  In mechanistic studies, they demonstrated the ability of plasma gelsolin to upregulate NOS3, an enzyme necessary for synthesis of reactive nitrogen intermediates necessary for intracellular bacterial killing.  Using murine models, the investigators demonstrated that pre-treatment with plasma gelsolin could improve host defense and protect mice against lethal bacterial pneumonia.  Clearly more work needs to be done to determine whether plasma gelsolin can have beneficial effects if given after infection, but there is one clinical scenario where bacterial infection can be predicted, and that is in the case of pneumonia which often occurs about a week following influenza infection.  This study suggests that patients at high risk for bacterial complication of influenza infection could be treated prophylactically with plasma gelsolin to improve their chances of surviving post-viral secondary pneumonia.  Thus, this is a particularly encouraging study for a major clinical problem.

Bethany Moore

Associate Editor

AJP-Lung