PULMONARY: Resolving acute lung injury with an agonist
Individuals with a number of clinical conditions, including pneumonia, and those treated by mechanical ventilation for a prolonged period of time are at risk of acute lung injury, a life-threatening disorder for which there is no treatment. It is hoped that understanding the natural processes by which acute lung injury spontaneously resolves in some individuals might provide new therapeutic targets. Thus, Holger Eltzschig and colleagues, at the University of Colorado Health Sciences Center, Denver, suggest that their observation in mice with ventilator-induced lung injury (VILI) implicate the protein A2BAR as a potential therapeutic target for acute lung injury.
In the study, mice lacking A2BAR were found to have reduced survival time and more severe VILI, when compared with normal mice. Consistent with this, normal mice treated with an A2BAR antagonist exhibited more severe lung damage than untreated mice, whereas an A2BAR agonist attenuated the severity of VILI. Further analysis revealed that one way in which the A2BAR agonists helped was by enhancing the clearance of fluid in the lungs (i.e., they helped dry out the lungs). These data indicate that agonists of A2BAR are likely to be part of the natural mechanism by which acute lung injury spontaneously resolves and might make good therapeutics.
TITLE: A2B adenosine receptor signaling attenuates acute lung injury by enhancing alveolar fluid clearance in mice
AUTHOR CONTACT:
Holger K. Eltzschig,
University of Colorado Health Sciences Center, Denver, Colorado, USA.
Phone: (303) 315-7320; Fax: (303) 315-0369; E-mail: holger.eltzschig@uchsc.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=34203
IMMUNOLOGY: New way for immune cells to enhance clearance of bacteria
Oliver Söhnlein and colleagues, at the Karolinska Institutet, Sweden, have identified a new function for a number of proteins secreted by human immune cells known as neutrophils or PMNs: they enhance the uptake of bacteria by other immune cells (known as macrophages) that are capable of destroying the microbes.
In the study, proteins secreted by human PMNs, specifically HBP and HNP1-3, were found to enhance the in vitro ability of human and mouse macrophages to take up bacteria coated in the immune molecule IgG. Mechanistically, HBP and HNP1-3 activated the macrophages to secrete soluble factors that, in turn, induced the macrophages to express proteins to which IgG can bind (CD32 and CD64). The authors therefore suggest that HBP and HNP1–3 secreted by PMNs have a role in clearing bacterial infections.
TITLE: Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages
AUTHOR CONTACT:
Oliver Söhnlein
Karolinska Institutet, Stockholm, Sweden.
Phone: 46-8-728-7212; Fax: 46-8-332047; E-mail: oliver.sohnlein@ki.se. or osoehnlein@ukaachen.de
View the PDF of this article at: https://www.the-jci.org/article.php?id=35740
Journal
Journal of Clinical Investigation