Effect of diabetes mellitus on endotoxin-induced lung injury

Joseph Keith Wright, Fiemu N. Nwariaku, Jason Clark, J. Cameron Falck, Thomas Rogers, Richard H. Turnage

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Objective: To examine the effects of diabetes mellitus on lipopolysaccharide (LPS)-induced pulmonary edema and alveolar neutrophil recruitment and activation. Hypothesis: Zucker diabetic fatty rats are resistant to the effects of intratracheal LPS on the extravasation of plasma proteins into the lungs. Design: Zucker diabetic fatty (ZDF) rats (genotype fa/fa) were used as a model of diabetes mellitus, while their normoglycemic heterozygous littermates served as controls. Lipopolysaccharide (Escherichia coli 0111: B4; 100-200 μg) or vehicle (0.25 mL of isotonic sodium chloride solution)was instilled into the airways of ZDF and control rats. Four hours later, pulmonary microvascular dysfunction was assessed by measuring the extravasation of Evans blue dye into the lung. Lipopolysaccharide-induced neutrophil recruitment was assessed by counting the number of neutrophils within the bronchoalveolar lavage fluid and measuring their expression of CD11b/CD18 by fluorescence-activated cell analysis sorting. Results: The LPS (200 μg) induced a 32% increase in Evans blue dye extravasation into the lungs of controls (P= .008) but had no such effect in diabetic animals. Pulmonary extravasation of Evans blue dye in controls was greater than that of ZDF rats both at baseline (P = .002) and in response to 200 μg of LPS (P<.001). The LPS upregulated neutrophil CD11b/CD18 expression in diabetic and nondiabetic groups and induced a greater than 50-fold increase in the number of neutrophils within the airways of both control and diabetic groups (P<.001). Conclusion: Despite the recruitment of a large number of neutrophils into the lung, the LPS-induced change in pulmonary microvascular permeability in diabetic animals is substantially less than that of nondiabetic controls.

Original languageEnglish (US)
Pages (from-to)1354-1359
Number of pages6
JournalArchives of Surgery
Volume134
Issue number12
DOIs
StatePublished - Dec 1999

ASJC Scopus subject areas

  • Surgery

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