ACTIVATION AND RECRUITMENT OF POLYMORPHONUCLEAR GRANULOCYTES DURING ACUTE LUNG INJURY FOLLOWING BLUNT CHEST TRAUMA

Abstract

Lung contusion and subsequent pulmonary failure is a frequent clinical scenario. However, the underlying pathomechanisms remain to be elucidated. In particular, the role of neutrophils following chest trauma remains unclear. Thus, we hypothesized that following lung contusion neutrophils are activated and get recruited into the lung, potentially mediating acute lung injury. To study this, male C3H/HeN mice were subjected to blunt chest trauma induced by a single blast wave or sham procedure. 0.5, 2, 12 and 24 hrs later, blood and bronchoalveolar lavage (BAL) were obtained. Circulating neutrophils were stained for CD11b, CD31 and CD62L as determined by FACS analysis. Lung leak was assessed by measuring total BAL protein; neutrophil influx was determined by quantifying BAL neutrophil content via cytospin and giemsa stain. MIP-2 concentration was measured in BAL by ELISA. As early as 0.5 hrs after the insult, total protein in BAL was markedly increased in trauma animals when compared to shams lasting until 24 hrs. Interestingly, neutrophil accumulation in BAL was also increased early after trauma starting at 2 hrs, which was in line with BAL MIP-2 levels peaking at the same time point. With regard to surface markers, a high percentage of neutrophils expressed CD62L (96%) and no differences were observed between sham and trauma animals. In contrast, CD11b experienced a marked though transient increase early at 0.5 hrs after the insult. CD31 peaked late at 24 hrs after chest trauma. Our data indicates that early following lung contusion the pulmonary endothelial barrier is compromised leading to protein leakage from the circulation. Simultaneously, lung contusion upregulates surface receptors on neutrophils necessary for their transmigration into the lung. This is associated with increased local chemokine levels. Further studies are needed to delineate the exact contribution of neutrophils in the pathogenesis of acute lung injury following blunt chest trauma (DFG KN 475/2-3).