Recruitment of neutrophils across the blood-brain barrier: the role of E- and P-selectins.
The adult central nervous system parenchyma is resistant to inflammation, but in juvenile rats the injection of inflammatory mediators, interleukin-1 beta for example, gives rise to extensive neutrophil recruitment and neutrophil-dependent blood-brain barrier breakdown. The factors that confer this resistant phenotype are unknown. In this study, the authors demonstrate that E- and P-selectin expression is increased to a similar extent in adult and juvenile brain after the intracerebral injection of IL-1 beta. Thus, the refractory nature of the brain parenchyma cannot be attributed to an absence of selectin expression. However, in injuries where the resistant characteristic of the brain parenchyma is compromised, and neutrophil recruitment occurs, selectin blockade may be an advantage. The authors investigated the contribution that selectins make to neutrophil recruitment during acute inflammation in the brain. The authors examined neutrophil recruitment by immunohistochemistry on brain sections of juvenile rats killed four hours after the intracerebral injection of IL-1 beta and the intravenous injection of neutralizing anti-selectin monoclonal antibodies (mAb). The administration of the P-selectin blocking mAb inhibited neutrophil recruitment by 85% compared with controls. Surprisingly, E-selectin blockade had no effect on neutrophil recruitment to the brain parenchyma. Thus, P-selectin appears to play a pivotal role in mediating neutrophil recruitment to the brain parenchyma during acute inflammation.
Bernardes-Silva
M
M
CNS Inflammation Group, School of Biological Sciences, Biomedical Sciences Building, University of Southampton, UK.
Anthony
D C
DC
Issekutz
A C
AC
Perry
V H
VH
D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D019040:E-Selectin / Q000032:analysis / Q000276:immunology*; D004660:Encephalitis / Q000276:immunology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology; D007797:Laminin / Q000032:analysis; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D019007:P-Selectin / Q000032:analysis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D007375:Interleukin-1; D007797:Laminin; D019007:P-Selectin