Leukocyte adherence contributes to disruption of the blood-brain barrier during activation of mast cells

William G. Mayhan

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The goal of this study was to examine the role of leukocytes in disruption of the blood-brain barrier during activation of mast cells using compound 48/80. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood-brain barrier (clearance of fluorescent-labeled dextran; molecular weight 10 000 daltons; FITC-dextran-10 K) was determined while suffusing with vehicle or compound 48/80 (10 or 25 μg/ml). During superfusion with vehicle (saline), clearance of FITC-dextran-10 K from pial vessels was modest and remained relatively constant during the experimental period (0.52±0.05 ml/sx10-6 at 80 min). In addition, diameter of pial arterioles remained constant (32±5 μm) while suffusing with vehicle. In contrast, topical application of compound 48/80 produced marked disruption of the blood-brain barrier to FITC-dextran-10 K. For example, suffusion with compound 48/80 (25 μg/ml) increased clearance of FITC-dextran-10 K about 4-fold to 2.26±0.25 ml/sx10-6 at 80 min. In addition, superfusion with compound 48/80 (25 μg/ml) constricted pial arterioles by 26±9% at 80 min. To determine a potential role for leukocyte adhesion to endothelium in disruption of the blood-brain barrier during suffusion with compound 48/80, we examined permeability during suffusion with compound 48/80 (25 μg/ml) in the presence of WT.3 (2 mg/kg i.v.), a monoclonal antibody directed against the functional epitope of the leukocyte adhesive glycoprotein (CD18; LFA-1β). We found that infusion of WT.3 markedly attenuated disruption of the blood-brain barrier to FITC-dextran-10 K in response to compound 48/80. The clearance of FITC-dextran-10 K during superfusion with compound 48/80 in the presence of WT.3 was 1.29±0.14 ml/sx10-6 at 80 min (P<0.05). Thus, the findings of the present study suggest that application of compound 48/80, to degranulate mast cells, activates the adhesion of leukocytes to cerebral venular endothelium which contributes to disruption of the blood-brain barrier. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)112-120
Number of pages9
JournalBrain Research
Volume869
Issue number1-2
DOIs
StatePublished - Jun 30 2000

Keywords

  • Anti-CD18
  • Brain
  • CD18
  • Cerebral venule
  • Compound 48/80
  • FITC-dextran
  • Mast cell
  • Monoclonal antibody
  • WT.3

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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