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L-selectin (CD62L) blockade does not impair peritoneal neutrophil emigration or subcutaneous host defense to bacteria
S R Sharar1, N N Chapman, L C Flaherty
1Department of Anesthesiology, University of Washington School of Medicine, Seattle 98195, USA.
Abstract:
Neutrophil (PMN) recruitment into systemic inflammatory sites in vivo is thought to be initiated by selectin-mediated endothelial adherence. We explored the role of L-selectin (CD62L) in leukocyte emigration following instillation of bacteria into the peritoneum or s.c. skin in rabbits. Pretreatment with blocking mAb against L-selectin (LAM1.3) reduced peritoneal PMN emigration 4 h after i.p. inoculation with 10(10) CFU of Escherichia coli by only 17% compared with animals receiving a nonblocking L-selectin mAb (LAM1.14). Peritoneal PMNs from saline-treated rabbits demonstrated a complete absence of L-selectin, whereas those from LAM1.3-treated animals retained 43% of their baseline L-selectin expression. This suggests that L-selectin shedding is not a requisite event for PMN emigration under these conditions. In rabbits given s.c. inoculations with either Staphylococcus aureus or E coli, pretreatment with mAb LAM1.3 did not significantly impair PMN emigration at 24 h, nor increase the incidence, size, or associated mortality of resulting abscesses at 7 days compared with animals receiving nonblocking mAb LAM1.14. We conclude that: 1) mAb blockade of L-selectin in vivo only modestly affects acute, E. coli-induced peritoneal PMN emigration; and 2) L-selectin blockade does not increase infectious sequelae associated with s.c. bacterial inoculation. These findings of only mildly reduced PMN emigration into the peritoneum and no alteration in s.c. host defense differ from those reported with L-selectin blockade under other, nonbacterial inflammatory conditions, and suggest that redundant selectin-mediated mechanisms (P- and E-selectin) are sufficient for normal PMN emigration in response to bacterial stimulation.
Insights
Blocking L-selectin (CD62L) in rabbits only modestly reduced neutrophil emigration during bacterial peritonitis. L-selectin blockade did not worsen outcomes of skin infections, suggesting redundant selectin pathways in bacterial inflammation.
Area of Science:
- Immunology
- Inflammation Biology
Background:
- Neutrophil (PMN) recruitment is crucial for host defense against bacterial infections.
- Selectin-mediated endothelial adherence is considered the initial step in leukocyte emigration.
Purpose of the Study:
- To investigate the role of L-selectin (CD62L) in rabbit leukocyte emigration during bacterial peritonitis and skin infections.
Main Methods:
- Rabbits were pretreated with blocking or non-blocking anti-L-selectin monoclonal antibodies (mAbs).
- Bacterial (Escherichia coli, Staphylococcus aureus) inoculation was performed intraperitoneally or subcutaneously.
- Neutrophil emigration, abscess formation, and mortality were assessed at various time points.
Main Results:
- Anti-L-selectin mAb treatment only modestly reduced peritoneal neutrophil emigration following E. coli inoculation (17% reduction).
- L-selectin shedding was not required for PMN emigration in this model.
- Subcutaneous bacterial inoculation with anti-L-selectin mAb did not impair neutrophil emigration or increase abscess severity or mortality.
Conclusions:
- L-selectin blockade has a limited impact on acute neutrophil emigration during bacterial peritonitis.
- L-selectin is not essential for controlling subcutaneous bacterial infections in rabbits.
- Redundant selectin mechanisms (P- and E-selectin) likely compensate for L-selectin blockade in bacterial-induced inflammation.