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 (Fe3+ TRF) can be quantitatively analyzed in blood and tissue samples with low-temperature EPR techniques. We hypothesized that use of EPR 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 (Fe3+)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 (Fe3+)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 CD11b adhesion molecules on the surface of PMNs during the first 24 h after SW induced injury. Sham-treated animals were used as control. Exposure to SW led to a significant decrease in the amount of blood (Fe3+)TRF that correlated with the extent of lung injury and developed gradually during the first 24 h. Thus, sequestration of (Fe3+)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+/-0.6 microM in controls to 7.5+/-1.3 microM in exposed animals. The levels of (Fe3+)TRF remained decreased throughout 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 of CD11b on the surface membrane of PMNs. Extensive release of cytokines IL-1, IL-6, MCP-1, and MIP-2 was observed in BAL fluid and blood plasma during 24 h postexposure. We conclude that EPR monitoring of blood (Fe3+)TRF can be a useful approach for assessment of systemic pro-inflammatory alterations due to SW-induced lung injury.