Natural killer cells activated through NKG2D mediate lung ischemia-reperfusion injury

AUTHORS

Daniel R. Calabrese, Emily Aminian, Benat Mallavia, Fengchun Liu, Simon J. Cleary, Oscar A. Aguilar, Ping Wang, Jonathan Hoover, Jonathan P. Singer, Steven R. Hays, Jeffrey A. Golden, Jasleen Kukreja, Daniel T. Dugger, Mary Nakamura, Lewis L. Lanier, Mark R. Looney, and John R. Greenland

ABSTRACT

Pulmonary ischemia-reperfusion injury (IRI) is a clinical syndrome of acute lung injury that occurs after lung transplantation or remote organ ischemia. IRI causes early mortality and has no effective therapies. While natural killer (NK) cells are innate lymphocytes capable of recognizing injured cells, their roles in acute lung injury are incompletely understood. Here, we demonstrated that NK cells were increased in frequency and cytotoxicity in two different IRI mouse models. We showed that NK cells trafficked to the lung tissue from peripheral reservoirs and were more mature within lung tissue. Acute lung ischemia-reperfusion injury was blunted in a NK cell-deficient mouse strain but restored with adoptive transfer of NK cells. Mechanistically, NK cell NKG2D receptor ligands were induced on lung endothelial and epithelial cells following IRI, and antibody-mediated NK cell depletion or NKG2D stress receptor blockade abrogated acute lung injury. In human lung tissue, NK cells were increased at sites of ischemia-reperfusion injury and activated NK cells were increased in prospectively collected human bronchoalveolar lavage in subjects with severe IRI. These data support a causal role for recipient peripheral NK cells in pulmonary IRI via NK cell NKG2D receptor ligation. Therapies targeting NK cells may hold promise in acute lung injury.

A comparison of two types of electrospun chitosan membranes and a collagen membrane in vivo

Electrospun chitosan membranes subjected to post-spinning processes using either triethylamine/tert-butyloxycarbonyl (TEA/tBOC) or butyryl-anhydride (BA) modifications to maintain nanofiber structure have exhibited potential for use in guided bone regeneration applications. The aim of this study was to evaluate ability of the modified membranes to support healing of bone-grafted defects as compared to a commercial collagen membrane.

Material properties of bighorn sheep (Ovis canadensis) horncore bone with implications for energy absorption during impacts

Bighorn sheep rams participate in high impact head-butting without overt signs of brain injury, thus providing a naturally occurring animal model for studying brain injury mitigation. Previously published finite element modeling showed that both the horn and bone materials play important roles in reducing brain cavity accelerations during ramming.

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Ablation of Enpp6 results in transient bone hypomineralization

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Biomineralization is a fundamental process key to the development of the skeleton. The phosphatase orphan phosphatase 1 (PHOSPHO1), which likely functions within extracellular matrix vesicles, has emerged as a critical regulator of biomineralization. The biochemical pathways which generate intravesicular PHOSPHO1 substrates are however currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase (ENPP6) is an upstream source of PHOSPHO1 substrate.

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A selected small molecule prevents inflammatory osteolysis through restraining osteoclastogenesis by modulating PTEN activity

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Inflammatory osteolysis is a severe infectious bone disorder that occurs during orthopaedic surgery and is caused by disruptions in the dynamic balance of bone matrix homeostasis, which makes this condition a burden on surgical procedures. Developing novel therapeutic drugs about inhibiting excessive osteoclastogenesis acts as an efficient approach to preventing inflammatory bone destruction.

Material properties of bighorn sheep (Ovis canadensis) horncore bone with implications for energy absorption during impacts

AUTHORS

Luca H.Fuller, Seth W.Donahue

ABSTRACT

Bighorn sheep rams participate in high impact head-butting without overt signs of brain injury, thus providing a naturally occurring animal model for studying brain injury mitigation. Previously published finite element modeling showed that both the horn and bone materials play important roles in reducing brain cavity accelerations during ramming. However, in that study the elastic modulus of bone was assumed to be similar to that of human bone since the modulus of ram bone was unknown. Therefore, the goal of this study was to quantify the mechanical properties, mineral content, porosity, and microstructural organization of horncore cortical bone from juvenile and adult rams. Mineral content and elastic modulus increased with horn size, and porosity decreased. However, modulus of toughness did not change with horn size. This latter finding raises the possibility that the horncore cortical bone has not adapted exceptional toughness despite an extreme loading environment and may function primarily as an interface material between the horn and the porous bone within the horncore. Thus, geometric properties of the horn and horncore, including the porous bone architecture, may be more important for energy absorption during ramming than the horncore cortical bone. Results from this study can be used to improve accuracy of finite element models of bighorn sheep ramming to investigate these possibilities moving forward.