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Intravenous lipopolysaccharide induces cyclooxygenase 2‐like immunoreactivity in rat brain perivascular microglia and meningeal macrophages
Author(s) -
Elmquist Joel K.,
Breder Christopher D.,
Sherin Jonathan E.,
Scammell Thomas E.,
Hickey William F.,
Dewitt David,
Saper Clifford B.
Publication year - 1997
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/(sici)1096-9861(19970505)381:2<119::aid-cne1>3.0.co;2-6
Subject(s) - microglia , biology , lipopolysaccharide , cyclooxygenase , immune system , central nervous system , circumventricular organs , inflammation , immunology , neuroscience , pathology , endocrinology , medicine , biochemistry , enzyme
Production of prostaglandins is a critical step in transducing immune stimuli into central nervous system (CNS) responses, but the cellular source of prostaglandins responsible for CNS signalling is unknown. Cyclooxygenase catalyzes the rate‐limiting step in the synthesis of prostaglandins and exists in two isoforms. Regulation of the inducible isoform, cyclooxygenase 2, is thought to play a key role in the brain's response to acute inflammatory stimuli. In this paper, we report that intravenous lipopolysaccharide (LPS or endotoxin) induces cyclooxygenase 2‐like immunoreactivity in cells closely associated with brain blood vessels and in cells in the meninges. Neuronal staining was not noticeably altered or induced in any brain region by endotoxin challenge. Furthermore, many of the cells also were stained with a perivascular microglial/macrophage‐specific antibody, indicating that intravenous LPS induces cyclooxygenase in perivascular microglia along blood vessels and in meningeal macrophages at the edge of the brain. These findings suggest that perivascular microglia and meningeal macrophages throughout the brain may be the cellular source of prostaglandins following systemic immune challenge. We hypothesize that distinct components of the CNS response to immune system activation may be mediated by prostaglandins produced at specific intracranial sites such as the preoptic area (altered sleep and thermoregulation), medulla (adrenal corticosteroid response), and cerebral cortex (headache and encephalopathy). J. Comp. Neurol. 381:119‐129, 1997. © 1997 Wiley‐Liss, Inc.