Cerebral and pial microvessels: differential expression of γ-glutamyl transpeptidase and alkaline phosphatase

Lawrenson, John G; Reid, A. R.; Finn, T; Orte, Carlos; Allt, G.

doi:10.1007/s004290050206

Cited by 32 publications

(17 citation statements)

References 19 publications

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“…The observed AP expression pattern was largely similar to that in rodents and primates as reported previously [40,41]. In contrast to Alzheimer’s disease [42], we did not find increased AP expression in MS brain compared to controls.…”

Section: Discussionsupporting

confidence: 90%

Endotoxin- and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation

Huizinga

Kreft

Onderwater

et al. 2012

J Neuroinflammation

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BackgroundAlkaline phosphatase (AP) is a ubiquitously expressed enzyme which can neutralize endotoxin as well as adenosine triphosphate (ATP), an endogenous danger signal released during brain injury. In this study we assessed a potential therapeutic role for AP in inhibiting neuroinflammation using three complementary approaches.MethodsMice were immunized to induce experimental autoimmune encephalomyelitis (EAE) and treated with AP for seven days during different phases of disease. In addition, serological assays to determine AP activity, endotoxin levels and endotoxin-reactive antibodies were performed in a cohort of multiple sclerosis (MS) patients and controls. Finally, the expression of AP and related enzymes CD39 and CD73 was investigated in brain tissue from MS patients and control subjects.ResultsAP administration during the priming phase, but not during later stages, of EAE significantly reduced neurological signs. This was accompanied by reduced proliferation of splenocytes to the immunogen, myelin oligodendrocyte glycoprotein peptide. In MS patients, AP activity and isoenzyme distribution were similar to controls. Although endotoxin-reactive IgM was reduced in primary-progressive MS patients, plasma endotoxin levels were not different between groups. Finally, unlike AP and CD73, CD39 was highly upregulated on microglia in white matter lesions of patients with MS.ConclusionsOur findings demonstrate that: 1) pre-symptomatic AP treatment reduces neurological signs of EAE; 2) MS patients do not have altered circulating levels of AP or endotoxin; and 3) the expression of the AP-like enzyme CD39 is increased on microglia in white matter lesions of MS patients.

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Section: Discussionsupporting

confidence: 90%

Endotoxin- and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation

Huizinga

Kreft

Onderwater

et al. 2012

J Neuroinflammation

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“…A faint staining for alkaline phosphatase, as revealed by application of the substrate p-nitrophenyl phosphate, persisted in part of the capillaries of NTPDase1-deficient mice. This is consistent with previous observations that identified alkaline phosphatase on capillaries involved in the formation of the blood-brain barrier [Lawrenson et al, 1999].…”

Section: Identification Of the Major Microglial Nucleoside Tri-and -Dsupporting

confidence: 93%

Microglial ectonucleotidases: Identification and functional roles

Braun

Zimmermann

2001

Drug Development Research

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Microglial cells represent resident macrophages of the central nervous system where they resume a resting state of unknown physiological function. They are rapidly transformed into an activated state by acute pathological events affecting the nervous system. Activated microglia function in tissue repair and regeneration but may also enhance tissue damage. Cultured microglial cells express both P2Y and P2X receptors. Activation of the microglial P2X 7 receptor can result in the release of cytokines or also mediate cytotoxicity in microglial cells. Microglial cells have developed mechanisms for controlling the surrounding concentrations of free extracellular ATP via a surface-expressed ectonucleotidase chain. We analyzed the expression of the ectonucleotidases associated with resting microglia and microglia activated by two models of cerebral ischemia. Out of a plethora of enzymes with the potential to hydrolyze extracellular nucleotides, the major ectonucleotidases associated with microglia are NTPDase1, which hydrolyzes ATP and ADP, and ecto-5′-nucleotidase, which catalyzes the hydrolysis of AMP to adenosine. This is shown by enzyme histochemical analysis, immunocytochemistry, Northern hybridization, and the analysis of NTPDase1-deficient mice. Our results suggest that a major function of resting microglia could be in the lowering of interstitial levels of ATP acting either via autocrine pathways or in the ATP-involving signaling pathways between adjacent neurons and astrocytes. Enhanced activity of NTPDase1 may protect microglia, activated by various pathological settings, from overstimulation by ATP released from the injured tissue. The parallel increase in activity of ecto-5′-nucleotidase would facilitate the formation of the final hydrolysis product adenosine that exerts neuromodulatory and immunomodulatory actions and contributes to the protection of neurons. Drug Dev. Res. 53:208-217, 2001.

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“…This is also in contrast to chick brain capillaries, which display alkaline phosphatase activity from the 3rd week of development (Stewart and Wiley 1981). Also, we failed to demonstrate g-GT activity at the endothelium of the glycogen body, which is easily detected at rat brain capillaries (Lawrenson et al 1999). In this respect, however, the chick glycogen body does not differ from brain capillaries of the same species that do not express g-GT activity as determined biochemically in isolated vessels (Nico et al 1997).…”

Section: Discussioncontrasting

confidence: 66%

The blood-brain barrier of the chick glycogen body (corpus gelatinosum) and its functional implications

Möller

Kummer

2003

Cell and Tissue Research

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Among recent vertebrates only birds possess a glycogen body (corpus gelatinosum), located in the rhomboidal sinus of the lumbosacral region of the spinal cord and separated from the neural tissue proper. Because of the specific topographical situation of this circumventricular organ, the structure of its vascular system is of special interest with respect to the still unsolved functional problems. The existence of a blood-brain barrier is demonstrated by the exclusion of intravascularly injected tracer (horseradish peroxidase), and immunocytochemical demonstration of glucose transporter-1 as a functional marker and of neurothelin, occludin and ZO-1 as structural markers. Alkaline phosphatase and gamma-glutamyltransferase activities, two enzyme reactions frequently used for demonstration of an established blood-brain barrier in vitro, were localized histochemically on the plasmalemma of glycogen body cells and were absent from the endothelium. In addition, local enlargements of the intercellular space were observed by transmission and scanning electron microscopy. In accordance with the concept of a third circulation the cerebrospinal fluid may be the vehicle for distributing substances originating in the glycogen body to the CNS, while the vascular endothelium maintains the internal milieu by virtue of its dynamic barrier functions.

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Cerebral and pial microvessels: differential expression of γ-glutamyl transpeptidase and alkaline phosphatase

Cited by 32 publications

References 19 publications

Endotoxin- and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation

Endotoxin- and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation

Microglial ectonucleotidases: Identification and functional roles

The blood-brain barrier of the chick glycogen body (corpus gelatinosum) and its functional implications

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