CD43Lo classical monocytes participate in the cellular immune response to isolated primary blast lung injury

Abstract

BackgroundExplosive blast trauma occurs by four mechanisms: primary injuries are due to the isolated effect of the blast wave on the human body, secondary injuries are due to damage from fragments energised from the explosion, tertiary injuries result from acceleration of the body against an object or through the explosion energising hard materials in a solid form (not fragments) and encroaching upon the person, and quaternary injuries describe other physical insults, including burns and smoke inhalation 1 .Gas-containing organs such as the lungs are particularly susceptible to barotrauma, and 'Primary Blast Lung Injury' (PBLI) is a commonly reported injury amongst blast casualties. A review of terrorist bombings worldwide found the incidence of PBLI in immediate fatalities to be as high as 47% 2 ; whilst in a review of military blast casualties that survived to emergency admission, PBLI was found in 11.2% of 648 blast casualties. In this series, 16.2% of mounted and 17.1% of dismounted injuries developed PBLI, which was significantly associated with increased mortality 3,4 .Laboratory investigations of PBLI have sought to recapitulate the injury under experimental conditions. Studies investigating the subsequent immune response have been reported most commonly in rats 5-10 , mice [11][12][13][14][15] and swine 16,17 . These studies have offered overwhelming evidence of the neutrophil response to PBLI in animal models, with increases in circulating and broncho-alveolar lavage fluid (BALF) neutrophils, increases in Myeloperoxidase (MPO) activity in the lung, and neutrophil staining by histology [9][10][11][12]14,18,19 . However, the immune response to tissue damage differs depending on the type of organ injured and their local physiology; it remains unclear what specific contribution blast injuries to different parts of the body make to the inflammatory response that ensues. Whilst most clinically blast injured patients are polytraumatised, discerning these interacting immune responses experimentally is necessary for translational studies seeking to better understand, monitor or attenuate the immune response in blast trauma.Further, knowledge of the role played by other immune cells to PBLI is limited -no study has characterised the full repertoire of immune cells in PBLI; specifically, the involvement of monocytes in PBLI remains unclear. These cells are frequently recruited to sites of inflammation; in humans they are characterised by differential CD14 and CD16 expression 20 , in mice by CCR2, CX3CR1 and Ly6C 21,22 and in rats by CD43 alone or in conjunction with His48 23 . In rats, CD43 Hi and Lo monocytes are considered to be analogous to the Ly6C Lo (Non-classical) and Ly6C Hi (Classical) murine monocytes respectively. Classical Ly6C Hi monocytes are recruited to tissues in sterile 24 and infectious 25 models of inflammation. There, they can differentiate into inflammatory macrophages and dendritic cells, amplifying or resolving inflammation. In rats, circulating monocyte subsets are activated by inflammator...

Microstructural Consequences of Blast Lung Injury Characterized with Digital Volume Correlation

“…In real terms, this equates to a small region ~0.1 mm 3 (Zone 1) that may be obviously damaged by the blast, potentially compromising a region 10 times that size in terms of the mechanics. The fact this is not observed throughout the specimen nor affecting the greater surrounding region of this lung volume (100% or full volume) supports the fact that this is a moderate-blast condition and a non-lethal dose (Barnett-Vanes et al, 2016).…”

“…Applied blast pressures (Figure 3) were in or below the level of the reported thresholds for lung injury (CR Bass et al, 2008). Previous research on BLI suggested the moderate blast case is survivable with no observable structural damage (Barnett-Vanes et al, 2016).…”

“…This moderate case is known to approach the upper bound of survivability in live animals (Barnett-Vanes et al, 2016). Therefore, this case was included in this cadaveric study to highlight any tissue changes that may have occurred (tissue stiffness), which are not visibly shown to be damaging, i.e., no hemorrhage, but may cause structural changes potentially visible in the strain fields.…”

“…All other organs were shielded from the blast (head, abdomen and limbs). The efficiency of blast wave isolation to a target region of the specimen has been established previously (Eftaxiopoulou et al, 2015;Barnett-Vanes et al, 2016). The high lung volume was used to replicate the pre-tension of breathing lung tissue during a blast event.…”

“…The opening for the specimen is adaptable to account for the small variations in size from animal to animal. The blast wave is isolated to the thorax alone and shielded distal to the thorax, leading to a repeatable loading conditions (Barnett-Vanes et al, 2016). Sensors 2 and 3 were installed on the loading platform above and below the incident blast pressure loading site of the specimen.…”