Effect of diabetes mellitus on endotoxin-induced lung injury.
OBJECTIVE
To examine the effects of diabetes mellitus on lipopolysaccharide (LPS)-induced pulmonary edema and alveolar neutrophil recruitment and activation.


OBJECTIVE
Zucker diabetic fatty rats are resistant to the effects of intratracheal LPS on the extravasation of plasma proteins into the lungs.


METHODS
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 microg) 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 microg) 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 microg 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).


CONCLUSIONS
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.
Wright
J K
JK
Department of Surgery, University of Texas Southwestern Medical School, Dallas 75235-9060, USA.
Nwariaku
F N
FN
Clark
J
J
Falck
J C
JC
Rogers
T
T
Turnage
R H
RH
D000818:Animals; D002199:Capillary Permeability / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D015633:Extravascular Lung Water / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008168:Lung / Q000098:blood supply; D008297:Male; D020556:Neutrophil Infiltration / Q000276:immunology; D011650:Pulmonary Alveoli / Q000276:immunology; D051381:Rats; D011924:Rats, Zucker; D012128:Respiratory Distress Syndrome / Q000276:immunology*; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*
D008070:Lipopolysaccharides