Secondary bacterial peritonitis continues to be a difficult problem for both patient and surgeon. Even with the advent of newer antibiotics, little improvement in mortality has been achieved. Within the internal milieu of the peritoneal cavity, host defense mechanisms normally should act to limit the growth and dispersion of invading microorganisms. We seek to obtain a better understanding of these host defenses both at the cellular level as well as in the entire animal. In particular, the aims of this grant are 1) to define the mechanism of the potentiating effect of hemoglobin in experimental peritonitis, 2) to determine the specific action of fibrinogen and fibrin in experimental peritonitis and intraperitoneal abscess formation. In the first case, the present evidence supports the idea that hemoglobin permits certain strains of E. coli to elaborate leukotoxins which inhibit the bacteriocidal function of neutrophils and monocytes. This, in turn, permits the bacteria to proliferate to lethal levels. In the second, fibrin and its breakdown products impair the bacteriocidal function of neutrophils and monocytes by a different mechanism, i.e. by impairing access to the bacteria by limiting the migration of host cells into contact with bacteria. To test these hypotheses, both in vivo and in vitro techniques will be necessary. For the first aim, the basic strategy is to isolate and characterize those products of the interaction between bacteria and hemoglobin which impair neutrophil function in vitro. These materials will then be tested in rats for their capacity to potentiate infections with bacterial strains which cannot be potentiated with hemoglobin itself. For the second aim, we plan to differentiate between the physical entrapment of neutrophils by fibrin, its chemical effects on the neutrophil and its alteration of the physiological milieu.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI014032-08
Application #
3125609
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1978-04-01
Project End
1990-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
8
Fiscal Year
1986
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
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