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Systemic LPS injection leads to granulocyte influx into normal and injured brain: Effects of ICAM-1 deficiency

Bohatschek, M; Werner, A; Raivich, G; (2001) Systemic LPS injection leads to granulocyte influx into normal and injured brain: Effects of ICAM-1 deficiency. EXP NEUROL , 172 (1) 137 - 152. 10.1006/exnr.2001.7764.

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Abstract

The lipopolysaccharide (LPS) constituents of the gram-negative bacterial wall are among the most potent activators of inflammation. In the current study, we examined the effect of subcutaneous injection of Escherichia coli LPS on leukocyte influx into the normal and injured brain using endogenous peroxidase (EP). Normal brain parenchyma does not contain granulocytes and this does not change after indirect trauma, in facial axotomy. However, systemic injection of 1 mg LPS led to a gradual appearance of EP-positive parenchymal granulocytes within 12 h, with a maximum at 1-4 days after injection. Facial axotomy (day 14) led to a further 50-300% increase in granulocyte number. Of the five mouse strains tested in the current study, four-Balb/C, FVB, C57B1/6, and C3H/N-showed vigorous granulocyte influx (60-90 cells per 20-mum section in axotomized facial nucleus, 20-40 cells per section on the contralateral side). The influx was an order of magnitude lower in the SJL mice. The peroxidase-positive cells were immunoreactive for neutrophil antigen 7/4 and alphaM beta2 integrin, were negative for IBA1 (monocytes) and CD3 (T cells), and could be prelabeled by subcutaneous injection with rhodamine B isothiocyanate (RITC), confirming their origin as blood-borne granulocytes. All RITC-positive cells were IBA1 negative. This influx of granulocytes was accompanied by a disruption of the blood-brain barrier to albumin and induction of the cell adhesion molecule ICAM-1 on affected blood vessels. Transgenic deletion of ICAM-1 led to a more than 50% reduction in the number of infiltrating granulocytes compared to litter-matched wild-type controls, in normal brain as well as in axotomized facial motor nucleus. In summary, systemic injection of LPS leads to invasion of granulocytes into the mouse brain and a breakdown of the blood-brain barrier to blood-borne cells and to soluble molecules. Moreover, this mechanism may play a pathogenic role in the etiology of meningitis and in severe bacterial sepsis. (C) 2001 Academic Press.

Type: Article
Title: Systemic LPS injection leads to granulocyte influx into normal and injured brain: Effects of ICAM-1 deficiency
DOI: 10.1006/exnr.2001.7764
Keywords: neutrophil granulocyte, septic shock, brain injury, extravasation, lipopolysaccharide, CENTRAL-NERVOUS-SYSTEM, FACIAL MOTOR NUCLEUS, TUMOR-NECROSIS-FACTOR, INTERCELLULAR-ADHESION MOLECULE-1, ACUTE INFLAMMATORY RESPONSE, NITRIC-OXIDE SYNTHASE, FACTOR-KAPPA-B, IN-VIVO, ENDOTHELIAL-CELLS, MICROGLIAL CELLS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health > Maternal and Fetal Medicine
URI: http://discovery.ucl.ac.uk/id/eprint/26095
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