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
