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Transgenic HbS Mouse Neutrophils in Increased Susceptibility to Acute Lung Injury*: Implications for Sickle Acute Chest Syndrome FREE TO VIEW

L. Hsu, MD, PhD; T. McDermott; L. Brown; S. M. Aguayo, MD, FCCP
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*From Atlanta Veterans Administration Medical Center and Emory University, Atlanta, GA.

Correspondence to: Lewis Hsu, MD, PhD, Emory University School of Medicine, 69 Butler St SE, Atlanta, GA 30303

Chest. 1999;116(suppl_1):92S-93S. doi:10.1378/chest.116.suppl_1.92S
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The sickle cell acute chest syndrome (ACS) has many clinical similarities to other forms of acute lung injury such as ARDS. We investigated a role for neutrophils in ACS pathophysiology, using a transgenic (Tg) mouse expressing human sickle hemoglobin that has mild features of sickle cell disease under baseline conditions.

After experimental acute lung insult, this Tg HbS mouse will have increased pulmonary neutrophils compared with normal mice given the same acute insult.

Mice received either oleic acid (OA) injection or sham injection of the tail vein, and 4 h later were exsanguinated with anesthetic overdose. To measure myeloperoxidase (MPO), as an indicator of the granulocytes present within the lungs, whole lungs were homogenized and the supernatant was assayed spectrophotometrically. For histochemical staining, lungs were fixed with formalin-acetone and embedded in paraffin.

The Tg HbS mice with OA injection (n = 7) had significantly higher MPO than normal mice with OA injection (n = 6) (0.038 compared with 0.018, p = 0.02). OA-injected mouse lungs have neutrophils infiltrating lung interstitium as well as neutrophils still within alveolar capillaries. Lung MPO did not correlate with granulocyte count, and total WBC counts were similar for Tg HbS and normal mice after OA.

Tg HbS mice have increased neutrophils after acute lung injury, compared to normal mice with the same OA insult. Despite the similar baseline conditions of lungs and neutrophils in Tg HbS mice, the presence of HbS is associated with susceptibility to acute lung injury. These animal model results may be a first step toward understanding the interaction between RBCs, endothelium, and WBCs in sickle-cell ACS.




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