Selectins mediate eosinophil recruitment in vivo: a comparison with their role in neutrophil influx.
The role of selectins in mediating eosinophil recruitment in vivo was assessed in a model of lipopolysaccharide (LPS)-induced mouse pleurisy. LPS administration resulted in significant eosinophil influx at 24 hours, whereas neutrophil recruitment to the cavity peaked at 4 hours and persisted for 24 hours. The anti-L-selectin monoclonal antibody (MoAb) MEL-14 effectively inhibited (by 97%) eosinophil influx at 24 hours and also inhibited neutrophil recruitment at both times (75% to 95%). Eosinophil recruitment was partially reduced (54%) by the anti-P-selectin MoAb 5H1 but, in contrast, was unaffected by the anti-E-selectin MoAb 10E6. Neutrophil influx at 4 or 24 hours was not affected by the anti-P- or anti-E-selectin MoAbs. However, coadministration of anti-P-selectin and anti-E-selectin was very effective at inhibiting eosinophil influx at 24 hours (86%) and neutrophil influx at 4 (93%) and 24 hours (92%). These results show that all three selectins play a role in LPS-induced eosinophil and neutrophil recruitment in vivo, although P- and E-selectin show a degree of functional redundancy. The demonstration that P-selectin mediates eosinophil but not neutrophil influx suggests that suppressing the function of this adhesion molecule may be beneficial in blocking eosinophil accumulation in pleural inflammation.
Henriques
G M
GM
Applied Pharmacology, National Heart & Lung Institute, London, UK.
Miotla
J M
JM
Cordeiro
S B
SB
Wolitzky
B A
BA
Woolley
S T
ST
Hellewell
P G
PG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D019040:E-Selectin / Q000276:immunology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D004731:Endotoxins / Q000633:toxicity; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000502:physiology*; D019041:L-Selectin / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000276:immunology / Q000502:physiology*; D010998:Pleurisy / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D004731:Endotoxins; D008070:Lipopolysaccharides; D019007:P-Selectin; D019041:L-Selectin; C044101:endotoxin, Escherichia coli