Recruitment of Neutrophils across the Blood–Brain Barrier: The Role of E- and P-selectins

Abstract

Summary:The adult central nervous system parenchyma is resistant to inflammation, but in juvenile rats the injection of inflammatory mediators, interleukin-1␤ 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␤. 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␤ 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.

A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI

“…Notably, leukocyte recruitment is often negligible (30), and little is known about adhesion of platelets in CM models. IL-1β and TNF both upregulate ICAM-1 (31, 32) and selectins (33,34) on the brain endothelium, and therefore, the differential binding of platelets to the brain endothelium following the microinjection of these cytokines into the brain was surprising. However, non-adhesion molecule-related vascular events, such as cytokine-induced volume changes, may play a role.…”

Inflammatory mechanisms involved in brain injury following cardiac arrest and cardiopulmonary resuscitation

“…IL-1β-positive staining was observed in the ischemic regions of the cortex within 16-24 h after stroke (80). An elevated level of IL-1β can potentiate inflammation by activating microglia and induce the infiltration of peripheral leukocytes by increasing the expression of adhesion molecules on endothelial cells; these events are associated with worsening of the infarct severity and progressive neurodegeneration (81)(82)(83). In addition to its role as a pro-inflammatory mediator, IL-1β can also elevate the expression of other pro-inflammatory cytokines, such as IL-6 and TNF-α, which can be upregulated following cerebral ischemia (84).…”

Brain-immune interactions in perinatal hypoxic-ischemic brain injury

“…All of selectins, including L-, P-, and E-selectin, participate in neutrophil rolling. However, in the immature brain, E-selectin appears to be less important as the blockade of E-selectin is not able to reduce the neutrophil recruitment to the brain inflammatory sites (Bernardes-Silva et al , 2001). By contrast, the administration of P- (but not L-) selectin neutralizing antibody inhibits neutrophil recruitment up to 85% compared to controls (Ley et al , 1995).…”