Balazs Toth

The role of γδ T cells in the regulation of neutrophil-mediated tissue damage after thermal injury

Thermal injury induces an inflammatory response that contributes to the development of secondary tissuedamage. Neutrophil recruitment and activation are in part responsible for this tissue damage. Although γδ T cells have been shown to regulate the inflammatory responses in tissues that are prone to neutrophil‐mediated injury post‐burn, their role in the induction of secondary tissue injury post‐burn remains unknown. To study this, γδ T cell‐deficient (γδ TCR−/−) and wild‐type (WT) mice were subjected to thermal injury or sham procedure, and tissue samples were isolated 1–24 h thereafter. Burn injury induced neutrophil accumulation in the lung and small intestines of WT mice at 1–3 h post‐injury. No such increase in neutrophil tissue content was observed in γδ TCR−/− mice. An increase in tissue wet/dry weight ratios was also observed in these organs at 3 h post‐burn in WT but not in γδ TCR−/− mice. A parallel increase in plasma and small intestine levels of the chemokines macrophage‐inflammatory protein‐1β (chemokine ligand 4) and keratinocyte‐derived chemokine (CXC chemokine ligand 1) were observed in injured WT mice but not in injured γδ TCR−/− mice. Increased activation (CD120b expression) of the circulating γδ T cell population was also observed at 3 h post‐burn in WT mice. These results indicate the γδ T cells, through the production of chemokines, play a central role in the initiation of neutrophil‐mediated tissue damage post‐burn.

Differential fluid regulation during and after soft tissue trauma and hemorrhagic shock in males and proestrus females

Gender differences in immune and organ functions have been described in different rodent models of trauma- and pressure-controlled hemorrhagic shock. We hypothesized that gender influences the regulation of plasma and tissue fluids in rats under such conditions. To study this we used male and weight matched proestrus female Sprague-Dawley rats, which were assigned to three groups (n = 7/group): sham, maximal bleedout (trauma and 45 min of blood pressure at 35 mmHg without resuscitation), or 5 h after completion of trauma–hemorrhage and resuscitation. Trauma-hemorrhage involved midline laparotomy and approx. 90 min of hemorrhagic shock (35 mmHg), followed by fluid resuscitation (4× the shed blood volume with Ringers lactate). 51Cr-EDTA, 125I-albumin distribution, and wet weight/dry weight were used to calculate plasma volume and extracellular fluid volume and cellular water content. Proestrus female rats showed significantly higher plasma volumes compared with weight-matched males. The volume of blood withdrawn in the first 15 min of hemorrhagic shock was significantly less in proestrus females compared with males; however, there was no significant difference in the total shed blood volume. Moreover, proestrus females showed less interstitial edema formation compared with male rats at 5 h after resuscitation. We conclude that differences in the regulation of plasma and tissue volumes exist between males and proestrus females during and after trauma-hemorrhage. The increased circulating blood volume could contribute the improved immune and organ functions in proestrus females under those conditions.

Differential alterations in intestinal permeability after trauma-hemorrhage.

BACKGROUND Recent studies have shown that the intestinal barrier function is altered and macromolecules can translocate after trauma and hemorrhagic shock. The translocated molecules are absorbed from the lymphatic tissue or directly enter the circulation in the gut. However, it remains unknown to what degree these compartments contribute to the clearance of the macromolecules. METHODS Male Sprague-Dawley rats (350-400 g) underwent a 5-cm midline laparotomy (i.e., soft tissue injury), were bled to a mean arterial pressure of 35 mmHg and maintained for approximately 90 min, and then resuscitated with Ringers lactate (4x the shed blood volume) over 60 min. At 2 h after resuscitation, a solution containing 51Cr-EDTA, FITC-dextran-4 kDa, and rhodamine B-dextran-40 kDa was instilled into a jejunal blind loop and their concentrations were determined in mesenteric lymph and blood samples harvested between 2 h and 4 h after resuscitation. RESULTS Trauma-hemorrhage and crystalloid resuscitation significantly increased mesenteric lymph flow and the mucosal permeability for the three marker molecules. There was no difference in the concentrations of 51Cr-EDTA between the blood and lymph compartment after trauma-hemorrhage. However, the high molecular weight marker (rhodamine-B-dextran-40 kDa) accumulated in significantly higher concentrations in the mesenteric lymph than in the plasma under such conditions. CONCLUSIONS The accumulation of macromolecules in the mesenteric lymph suggests that this compartment plays an important role in the altered gut barrier function after trauma-hemorrhage.