The sickle cell acute chest syndrome (ACS) has many clinical similarities to other forms of acute lung injury such as acute respiratory distress syndrome. Much pulmonary research implicates neutrophils as mediators of acute lung injury. We investigated a role for neutrophils in ACS pathophysiology, using a transgenic mouse expressing human sickle hemoglobin (βs HbbMDD) that has mild features of sickle cell disease.HYPOTHESIS: After experimental acute lung injury insult, this transgenic sickle mouse will have increased pulmonary neutrophils compared to normal mice given the same acute insult. METHODS: Mice were given either oleic acid injection (OA) or sham injection, and then euthanized 4 hours later with anesthetic overdose and exsanguination. Saline perfusion of the right heart further cleared the pulmonary circulation of blood. Lungs were then excised, homogenized, and assayed for the presence of myeloperoxidase enzyme (MPO), as an indicator of the granulocyte content of the lungs.RESULTS: The Tg HbS mice with OA injection (n=7) had higher MPO assay than normal mice with OA injection (n=6) (0.038 compared to 0.018, p=.023 by two-tailed t-test). Histochemical staining demonstrates that OA-injected mouse lungs have neutrophils infiltrating lung interstitium as well as neutrophils still within alveolar capillaries, while sham-injected mouse lungs have few neutrophils present. There was a poor correlation of lung MPO assay result and granulocyte count, with r2= 0.003 for n=18. Total WBC counts were similar for Tg HbS and normal mice after OA injection (6,500/mm3 and 7,400/mm3). These OA-injected WBC counts were higher than the sham-injected mice, indicating that the OA acute lung injury does induce an inflammatory response. CONCLUSION: Tg HbS mice have increased neutrophils after acute lung injury due to OA injection, compared to normal mice with the same OA insult. Despite the apparently normal baseline conditions of lungs and neutrophils in Tg HbS mice, the presence of sickle hemoglobin is associated with susceptibility to acute lung injury. These animal model results may be a first step toward an understanding of the interaction of RBC and WBC in sickle ACS. Mild decreases in WBC may be part of the therapeutic effect of hydroxyurea in preventing ACS.