Pro-Inflammatory Alterations and Status of Blood Plasma Iron in a Model of Blast-Induced Lung Trauma

Abstract

Impact of blast shock waves (SW) with the body wall produces blast lung injuries characterized by bilateral traumatic hemorrhages. Such injuries often have no external signs, are difficult to diagnose, and therefore, are frequently underestimated. Predictive assessment of acute respiratory distress syndrome outcome in SW-related accidents should be based on experimental data from appropriate animal models. Blood plasma transferrin is a major carrier of blood iron essential for proliferative "emergency" response of hematopoietic and immune systems as well as injured tissue in major trauma. Iron-transferrin complexes ([Fe 3+]TRF) can be quantitatively analyzed in blood and tissue samples with low-temperature EPR techniques. We hypothesized that use ofEPR techniques in combination with assays for pro-inflammatory cytokines and granulocytes in the peripheral blood and BAL would reveal a pattern of systemic sequestration of [Fe 3+]TRF that could be useful for development of biomarkers of the systemic inflammatory response to lung injury. With this goal we (i) analyzed time-dependent dynamics of [Fe 3+]TRF in the peripheral blood of rats after impacts of SW generated in a laboratory shock-tube and (ii) assayed the fluctuation of granulocyte (PMN) counts and expression of CDllb adhesion molecules on the surface of PMNs during the first 24 h after SWinduced injury. Sham-treated animals were used as control. Exposure to sw led to a significant decrease in the amount of blood [FeJ+]TRFthat correlated with the extent oflung injury and developed gradually during the first 24 h. Thus, sequestration of [FeJ+]TRF occurred as early as 3 h post-exposure. At that time, the steady state concentration of [Fe3+]TRF in blood samples decreased from 19.7±O.6~M in controls to 7.5±1.3 11M in exposed animals. The levels of [Fe 3+]TRF remained decreased thoughout the entire study period. PMN counts increased 5-fold and 3.5-fold over controls respectively, at 3 and 6 h postexposure. These effects were accompanied by an increase in expression ofCDllb on the surface membrane ofPMNs. Extensive release of cytokines IL-l, IL-6, MCP-l, and MIP-2 was observed in BAL fluid and blood plasma during 24 h postexposure. We conclude that EPR monitoring of blood [Fe 3+]TRF can be a useful approach for assessment of systemic pro-inflammatory alterations due to SW-induced lung injury.Detonation of explosives generates blast shock waves (SW) which are usually characterized by (i) amplitude of blast overpressure, (ii) frequency of sound, and (iii) kinetic energy of striking force, and are considered to be major factors that produce the blastinjured casualty (l -4). A pattern of striking injuries ranges from displacement and rupture of bone and organs to amputations oflimbs and can be assessed by the existing biomechanical models for high-velocity, low-mass impacts (l, 5-6). The effects produced by SW-generated sound and SW-generated overpressure are more complex and remain beyond the framework of predictive biomechanical models. These damaging effects of...

The epidemiology of blast lung injury during recent military conflicts: a retrospective database review of cases presenting to deployed military hospitals, 2003–2009

“…This in turn leads to leucocyte accumulation and subsequently epithelial cell damage (at 12 -24 h), endothelial cell damage (24 -56 h) and the late oedema typical of adult respiratory distress syndrome (ARDS). Histological examination reveals prominent perivascular oedema and extensive alveolar haemorrhage during the first 12 h, and thereafter, epithelial cell damage with detachment from the basement membrane [10]. The extent of lung damage is related to the magnitude of the blast exposure, with effects ranging from subclinical microscopic petechiae to large areas of confluent frank haemorrhage.…”

Inhibitory effect of quercetin on tryptase and interleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line

“…Quercetin might have such modulating properties on mast cells: as mast cell secretion products have some effects that promote and others that suppress inflammation, quercetin may reduce the release of pro-inflammatory mediators or even favour the release of anti-inflammatory ones. The inhibition of HDC mRNA transcription and tryptase and IL-6 generation by quercetin on mast cells may be useful in many pathological conditions associated with a chronic inflammation status such as MS, AD, cancer and allergies [46][47][48][49][50][51][52][53][54][55][56].…”

Spatial Coordination of Cell-Adhesion Molecules and Redox Cycling of Iron in the Microvascular Inflammatory Response to Pulmonary Injury

“…For this purpose, frozen sections of hemorrhagic foci and identical lung sites from sham-treated animals were disintegrated under liquid nitrogen and subjected to lysis in a buffer containing 10 mM EDTA, 150 mM NaCl, 50 mM Tris HCl (pH 7.5), 1% Triton X-100, 0.1% SDS, and a mixture of protease inhibitors (5 µg/ml aprotinin, 10 µM leupeptin, 2 mM EDTA, and 1 mM phenylmethylsulfonyl fluoride). The further protein separations and immunobloting were conducted as described previously (13). The primary antibodies used for hybridization were: mouse anti-ICAM-1 IgG (Santa Cruz Biotechnology, Inc., Santa Cruz, CA; www.scbt.com).…”

“…The obtained lung specimens (see earlier) were processed for the immunofluorescence imaging, as described previously (13). In brief, the tissue sections were washed with PBS, incubated in PBS containing 2% paraformaldehyde and 0.1% Triton X-100 for 20 min, washed 3 times with PBS, and then once with PBS containing 0.5% BSA and 0.15% glycine (buffer A).…”

“…Using a model of hemorrhagic pulmonary contusion, we demonstrated recently that the lung trauma is associated with recruitment and extravasation of the inflammatory PLCs, accumulation of extracellular myeloperoxidase (MPO), development of nitroxidative stress to EC, and upregulation of antioxidant proteins such as superoxide dismutase (SOD-II) and heme oxygenase (HO-1) that occur in time-dependent manner (13).…”