Alcohol abuse is a major predisposing factor for pneumonia caused by Streptococcus pneumoniae. Reasons for the increased incidence and severity of pneumonia in alcoholics are poorly understood. We have developed a model of pneumococcal pneumonia using a well characterized regimen of chronic ethanol feeding to study the alterations in host defense mechanisms that contribute to increased pneumococcal infections in alcoholics. Initial studies demonstrated that ethanol feeding for seven days significantly increased the fatality rate of type 3 pneumococcal pneumonia in this model. Phagocytosis and intracellular killing of pneumococci by neutrophils were markedly reduced at this time, and this reduction correlated with alterations in pulmonary bacterial clearance mechanisms. The studies proposed in this application will further characterize the effects of chronic ethanol ingestion on phagocytosis and killing by neutrophils by determining the effects of prolonged ethanol feeding on the severity of these alterations and recovery after discontinuation of the ethanol diet. Using inhibitors of ethanol metabolism, we will determine the involvement of acetaldehyde in alterations of neutrophil function. Studies will be performed to determine whether impaired phagocytosis is related to an abnormality in bacterial adherence of pneumococci to neutrophil receptors or impaired ingestion of receptor-bound bacteria. Alterations in adherence will be further investigated using flow cytometry to determine whether ethanol decreases the expression of neutrophil receptors for opsonized bacteria. Impaired ingestion may be due to ethanol-induced alterations of intracellular biochemical events such as reduction in diacylglycerol production or elevation of cyclic - 3', 5 - adenosine monophosphate (cAMP). These studies will provide valuable information about the mechanisms by which chronic ethanol ingestion alters neutrophil functions that are critical for recovery from bacterial infections.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AA009173-04
Application #
3452936
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1992-02-01
Project End
1996-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Rubins, J B; Charboneau, D; Prigge, W et al. (1996) Ethanol ingestion reduces antipneumococcal activity of rat pulmonary surfactant. J Infect Dis 174:507-12