Increased endothelialmicropakncles(emp) and platelet activation in mutliple sclerosis (ms) in exacerbation and presence of factor in ms plasma inducing emp generation in vitro

A. Minagar, Wenche Jy, Joaquin J Jimenez, L. M. Mauro, L. L. Horstman, W. W. Mao, William Sheremata, Yeon Ahn

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

In MS, breaching of the blood brain barrier allows transmigration of inflammatory cells across the endothelial barrier to form multifocal demyelinating lesions in CNS. MS is characterized by recurring exacerbations and remissions but factors responsible for exacerbations are unclear, elevated soluble adhesion molecules, sICAM-1, sVCAM-1, in exacerbation have been described, indicating endothelial disturbance in exacerbation. The difficulty of access to endothelium hampers its direct study. However, endothelial microparticles (EMP) are released during activation or apoptosis of endothelieal cells (EC). To assess endothelial dysfunction, we measured EMP in patients (pts) with MS, simultaneously with platelet microparticles (PMP). Additionally, for in vitro study, effect of MS plasma on EC was investigated. Methods. For clinical study. 30 pts with MS in exacerbation and 20 in remission were compared with 48 controls. Platelet-poor plasma was incubated with FITC-labeled anti-CD31 (anti-PECAM-1, marker of endothelia) and PE-labeled anti-CD42 (platelet marker) and examined by Coulter XL flow cytometer. Another endothelial marker, CD51, was also used. CD31+/CD42- or CD51+ particles were counted as EMP; CD31-/CD42+ were taken as PMP. For in vitro study, plasma from MS pts was incubated with microvascular endothelial cell (MVEC) culture and released EMP were assayed in supernate. Results. (1) Plasma from 30 pts in exacerbation had 3-5 fold increased CD31+ EMP compared to remission or normal controls, p<0.001. (2) PMP were also elevated in exacerbation compared to remission, p<0.01, indicating that EMP elevation is associated with platelet activation. (3) There was a significant correlation between elevation of EMP+CD31 and presence of gadolinium enhancing lesions in MRI. (4) Assay of CD51+ EMP showed modest but persistent elevation in both exacerbation and remission. (5) Plasma from MS pts induced release of CD31+ EMP from MVEC. Conclusions CD31+EMP is markedly elevated in pts with MS in exacerbation. It is associated with platelet activation and correlates well with gadolinium enhancement in MRI. This finding further supports association between endothelial dysfunction and exacerbation in MS. The assay method described is convenient for monitoring endothelial acrtivation in MS. Furthermore, plasma from MS induced shedding of EMP from MVEC culture. These findings indicate that a soluble factor in plasma induces endothelial dysfunction to release BMP and may be responsible for pathogenesis of MS.

Original languageEnglish
JournalBlood
Volume96
Issue number11 PART I
StatePublished - Dec 1 2000

Fingerprint

Platelet Activation
Sclerosis
Platelets
Chemical activation
Plasmas
Blood Platelets
Endothelial cells
Endothelial Cells
Gadolinium
Cell culture
Magnetic resonance imaging
Endothelium
Assays
Cell Culture Techniques
CD31 Antigens
Fluorescein-5-isothiocyanate
In Vitro Techniques
Blood-Brain Barrier
Adhesion
Association reactions

ASJC Scopus subject areas

  • Hematology

Cite this

Increased endothelialmicropakncles(emp) and platelet activation in mutliple sclerosis (ms) in exacerbation and presence of factor in ms plasma inducing emp generation in vitro. / Minagar, A.; Jy, Wenche; Jimenez, Joaquin J; Mauro, L. M.; Horstman, L. L.; Mao, W. W.; Sheremata, William; Ahn, Yeon.

In: Blood, Vol. 96, No. 11 PART I, 01.12.2000.

Research output: Contribution to journalArticle

@article{59de36acf7254382809a8e60739c8ee1,
title = "Increased endothelialmicropakncles(emp) and platelet activation in mutliple sclerosis (ms) in exacerbation and presence of factor in ms plasma inducing emp generation in vitro",
abstract = "In MS, breaching of the blood brain barrier allows transmigration of inflammatory cells across the endothelial barrier to form multifocal demyelinating lesions in CNS. MS is characterized by recurring exacerbations and remissions but factors responsible for exacerbations are unclear, elevated soluble adhesion molecules, sICAM-1, sVCAM-1, in exacerbation have been described, indicating endothelial disturbance in exacerbation. The difficulty of access to endothelium hampers its direct study. However, endothelial microparticles (EMP) are released during activation or apoptosis of endothelieal cells (EC). To assess endothelial dysfunction, we measured EMP in patients (pts) with MS, simultaneously with platelet microparticles (PMP). Additionally, for in vitro study, effect of MS plasma on EC was investigated. Methods. For clinical study. 30 pts with MS in exacerbation and 20 in remission were compared with 48 controls. Platelet-poor plasma was incubated with FITC-labeled anti-CD31 (anti-PECAM-1, marker of endothelia) and PE-labeled anti-CD42 (platelet marker) and examined by Coulter XL flow cytometer. Another endothelial marker, CD51, was also used. CD31+/CD42- or CD51+ particles were counted as EMP; CD31-/CD42+ were taken as PMP. For in vitro study, plasma from MS pts was incubated with microvascular endothelial cell (MVEC) culture and released EMP were assayed in supernate. Results. (1) Plasma from 30 pts in exacerbation had 3-5 fold increased CD31+ EMP compared to remission or normal controls, p<0.001. (2) PMP were also elevated in exacerbation compared to remission, p<0.01, indicating that EMP elevation is associated with platelet activation. (3) There was a significant correlation between elevation of EMP+CD31 and presence of gadolinium enhancing lesions in MRI. (4) Assay of CD51+ EMP showed modest but persistent elevation in both exacerbation and remission. (5) Plasma from MS pts induced release of CD31+ EMP from MVEC. Conclusions CD31+EMP is markedly elevated in pts with MS in exacerbation. It is associated with platelet activation and correlates well with gadolinium enhancement in MRI. This finding further supports association between endothelial dysfunction and exacerbation in MS. The assay method described is convenient for monitoring endothelial acrtivation in MS. Furthermore, plasma from MS induced shedding of EMP from MVEC culture. These findings indicate that a soluble factor in plasma induces endothelial dysfunction to release BMP and may be responsible for pathogenesis of MS.",
author = "A. Minagar and Wenche Jy and Jimenez, {Joaquin J} and Mauro, {L. M.} and Horstman, {L. L.} and Mao, {W. W.} and William Sheremata and Yeon Ahn",
year = "2000",
month = "12",
day = "1",
language = "English",
volume = "96",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "11 PART I",

}

TY - JOUR

T1 - Increased endothelialmicropakncles(emp) and platelet activation in mutliple sclerosis (ms) in exacerbation and presence of factor in ms plasma inducing emp generation in vitro

AU - Minagar, A.

AU - Jy, Wenche

AU - Jimenez, Joaquin J

AU - Mauro, L. M.

AU - Horstman, L. L.

AU - Mao, W. W.

AU - Sheremata, William

AU - Ahn, Yeon

PY - 2000/12/1

Y1 - 2000/12/1

N2 - In MS, breaching of the blood brain barrier allows transmigration of inflammatory cells across the endothelial barrier to form multifocal demyelinating lesions in CNS. MS is characterized by recurring exacerbations and remissions but factors responsible for exacerbations are unclear, elevated soluble adhesion molecules, sICAM-1, sVCAM-1, in exacerbation have been described, indicating endothelial disturbance in exacerbation. The difficulty of access to endothelium hampers its direct study. However, endothelial microparticles (EMP) are released during activation or apoptosis of endothelieal cells (EC). To assess endothelial dysfunction, we measured EMP in patients (pts) with MS, simultaneously with platelet microparticles (PMP). Additionally, for in vitro study, effect of MS plasma on EC was investigated. Methods. For clinical study. 30 pts with MS in exacerbation and 20 in remission were compared with 48 controls. Platelet-poor plasma was incubated with FITC-labeled anti-CD31 (anti-PECAM-1, marker of endothelia) and PE-labeled anti-CD42 (platelet marker) and examined by Coulter XL flow cytometer. Another endothelial marker, CD51, was also used. CD31+/CD42- or CD51+ particles were counted as EMP; CD31-/CD42+ were taken as PMP. For in vitro study, plasma from MS pts was incubated with microvascular endothelial cell (MVEC) culture and released EMP were assayed in supernate. Results. (1) Plasma from 30 pts in exacerbation had 3-5 fold increased CD31+ EMP compared to remission or normal controls, p<0.001. (2) PMP were also elevated in exacerbation compared to remission, p<0.01, indicating that EMP elevation is associated with platelet activation. (3) There was a significant correlation between elevation of EMP+CD31 and presence of gadolinium enhancing lesions in MRI. (4) Assay of CD51+ EMP showed modest but persistent elevation in both exacerbation and remission. (5) Plasma from MS pts induced release of CD31+ EMP from MVEC. Conclusions CD31+EMP is markedly elevated in pts with MS in exacerbation. It is associated with platelet activation and correlates well with gadolinium enhancement in MRI. This finding further supports association between endothelial dysfunction and exacerbation in MS. The assay method described is convenient for monitoring endothelial acrtivation in MS. Furthermore, plasma from MS induced shedding of EMP from MVEC culture. These findings indicate that a soluble factor in plasma induces endothelial dysfunction to release BMP and may be responsible for pathogenesis of MS.

AB - In MS, breaching of the blood brain barrier allows transmigration of inflammatory cells across the endothelial barrier to form multifocal demyelinating lesions in CNS. MS is characterized by recurring exacerbations and remissions but factors responsible for exacerbations are unclear, elevated soluble adhesion molecules, sICAM-1, sVCAM-1, in exacerbation have been described, indicating endothelial disturbance in exacerbation. The difficulty of access to endothelium hampers its direct study. However, endothelial microparticles (EMP) are released during activation or apoptosis of endothelieal cells (EC). To assess endothelial dysfunction, we measured EMP in patients (pts) with MS, simultaneously with platelet microparticles (PMP). Additionally, for in vitro study, effect of MS plasma on EC was investigated. Methods. For clinical study. 30 pts with MS in exacerbation and 20 in remission were compared with 48 controls. Platelet-poor plasma was incubated with FITC-labeled anti-CD31 (anti-PECAM-1, marker of endothelia) and PE-labeled anti-CD42 (platelet marker) and examined by Coulter XL flow cytometer. Another endothelial marker, CD51, was also used. CD31+/CD42- or CD51+ particles were counted as EMP; CD31-/CD42+ were taken as PMP. For in vitro study, plasma from MS pts was incubated with microvascular endothelial cell (MVEC) culture and released EMP were assayed in supernate. Results. (1) Plasma from 30 pts in exacerbation had 3-5 fold increased CD31+ EMP compared to remission or normal controls, p<0.001. (2) PMP were also elevated in exacerbation compared to remission, p<0.01, indicating that EMP elevation is associated with platelet activation. (3) There was a significant correlation between elevation of EMP+CD31 and presence of gadolinium enhancing lesions in MRI. (4) Assay of CD51+ EMP showed modest but persistent elevation in both exacerbation and remission. (5) Plasma from MS pts induced release of CD31+ EMP from MVEC. Conclusions CD31+EMP is markedly elevated in pts with MS in exacerbation. It is associated with platelet activation and correlates well with gadolinium enhancement in MRI. This finding further supports association between endothelial dysfunction and exacerbation in MS. The assay method described is convenient for monitoring endothelial acrtivation in MS. Furthermore, plasma from MS induced shedding of EMP from MVEC culture. These findings indicate that a soluble factor in plasma induces endothelial dysfunction to release BMP and may be responsible for pathogenesis of MS.

UR - http://www.scopus.com/inward/record.url?scp=33748637372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748637372&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33748637372

VL - 96

JO - Blood

JF - Blood

SN - 0006-4971

IS - 11 PART I

ER -