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P-selectin blockade does not impair leukocyte host defense against bacterial peritonitis and soft tissue infection in
S R Sharar1, S S Sasaki, L C Flaherty
1Department of Anesthesiology, University of Washington School of Medicine, Seattle.
Abstract:
Adhesion molecules are responsible for PMN-endothelial cell interactions involved in both PMN-mediated endothelial injury (e.g., after ischemia-reperfusion injury) and PMN-mediated host defense against bacterial infection. Inhibition of PMN-endothelial adherence with CD18 and P-selectin mAb has been shown to ameliorate the tissue injury resulting from ischemia and reperfusion under a variety of experimental conditions. However, interference with PMN function may result in an increased risk of bacterial infection. Previous investigations suggest that CD18 blockade can lead to increased infectious risk. Little is known of the infectious risks associated with selectin blockade. We report the effects of P-selectin blockade (using mAb PB1.3) on bacteria-induced PMN emigration into the peritoneum and subcutaneous (s.c.) tissue in rabbits. Leukocyte and PMN emigration into the peritoneum 4 h after inoculation with 10 ml of 10(9) CFU/ml Escherichia coli was significant in saline-treated animals, and not different in animals pretreated with mAb PB1.3. Similarly, the incidence and severity of abscess formation 7 days after s.c. inoculation with Staphylococcus aureus (10(7), 10(8), or 10(9) CFU) was not increased in rabbits pretreated with mAb PB1.3 compared to saline. PMN emigration to the s.c. S. aureus was also similar in both saline and mAb PB1.3-treated animals, as determined by light microscopy. We conclude that P-selectin blockade with mAb PB1.3: 1) does not interfere with acute, E. coli-induced PMN emigration into the peritoneum, 2) does not increase the incidence or severity of S. aureus abscess formation in s.c. tissue, and 3) interferes less with PMN antibacterial host defense mechanisms than inhibition of CD18-mediated PMN adherence.
Insights
Blocking P-selectin with mAb PB1.3 does not impair the body's ability to fight bacterial infections. This study found no increased risk of infection or abscess formation, suggesting P-selectin blockade is safer than CD18 blockade for host defense.
Area of Science:
- Immunology
- Cell Biology
- Infectious Diseases
Background:
- Adhesion molecules mediate polymorphonuclear leukocyte (PMN)-endothelial cell interactions crucial for host defense and tissue injury.
- Inhibiting PMN adherence with CD18 or P-selectin monoclonal antibodies (mAbs) can reduce ischemia-reperfusion injury.
- However, blocking PMN function may increase infection risk, with CD18 blockade linked to higher infectious risk, while selectin blockade risks are less understood.
Purpose of the Study:
- To investigate the effects of P-selectin blockade using mAb PB1.3 on bacteria-induced PMN emigration and host defense against bacterial infection in rabbits.
- To compare the infectious risks associated with P-selectin blockade versus CD18 blockade.
Main Methods:
- Rabbits were pretreated with either mAb PB1.3 or saline.
- PMN emigration into the peritoneum was assessed 4 hours after inoculation with Escherichia coli.
- Abscess formation and PMN emigration into subcutaneous tissue were evaluated 7 days after inoculation with Staphylococcus aureus.
Main Results:
- mAb PB1.3 did not alter PMN emigration into the peritoneum following E. coli inoculation compared to saline controls.
- The incidence and severity of S. aureus-induced abscess formation were not increased in rabbits treated with mAb PB1.3.
- PMN emigration to subcutaneous S. aureus was similar in both mAb PB1.3 and saline-treated groups.
Conclusions:
- P-selectin blockade with mAb PB1.3 does not impede acute PMN emigration into the peritoneum during E. coli infection.
- P-selectin blockade does not exacerbate S. aureus-induced abscess formation.
- mAb PB1.3 appears to interfere less with PMN antibacterial host defense mechanisms compared to CD18-mediated adherence inhibition.