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(Chest. 1999;116:92S-93S.)
© 1999 American College of Chest Physicians

Transgenic HbS Mouse Neutrophils in Increased Susceptibility to Acute Lung Injury*

Implications for Sickle Acute Chest Syndrome

L. Hsu, MD, PhD; T. McDermott; L. Brown and S. M. Aguayo, MD, FCCP

* 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

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.

Hypothesis

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

Materials and Methods

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.

Results

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.

Conclusion

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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 Canadian J. AnesthesiaHome page
P. G. Firth, Y. Tsuruta, Y. Kamath, W. H. Dzik, C. S. Ogilvy, and R. A. Peterfreund
Transfusion-related acute lung injury or acute chest syndrome of sickle cell disease? - A case report: [Une etude de cas : lesion pulmonaire aigue post-transfusionnelle ou syndrome pulmonaire aigu de la drepanocytose ?]
Can J Anesth, November 1, 2003; 50(9): 895 - 899.
[Abstract] [Full Text] [PDF]

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