Distribution of Immunoglobulin Superfamily Members ICAM-1, -2, -3, and the β2 Integrin LFA-1 in Multiple Sclerosis Lesions

Bø, Lars Eirik; Peterson, John W.; Mörk, Sverre; Hoffman, Patricia A.; Gallatin, Michael; Ransohoff, Richard M.; Trapp, Bruce D.

doi:10.1097/00005072-199610000-00006

Cited by 15 publications

(17 citation statements)

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“…4I). In addition, a fraction of parenchymal microvessels in histologically normal brains was ICAM-1 positive as reported (18).…”

Section: Icam-1 Expression On Cns Endothelial Cellssupporting

confidence: 56%

“…ICAM-1 is expressed on resting endothelium in various tissues including parenchymal vessels in noninflamed human brain (18,31). ICAM-1 mediates firm arrest of circulating T cells through binding of lymphocyte function-associated antigen 1 (integrin ␣ L ␤ 2 ), which is expressed by a majority of CSF T cells from both healthy volunteers and patients with CNS inflammation, and on virtually all CNS-infiltrating leukocytes in inflammatory multiple sclerosis lesions (18,32,33). ICAM-1 was constitutively expressed in the choroid plexus of healthy mice and mediated binding of lymphocytes in vitro with a StamperWoodroof assay (34,35).…”

Section: Discussionmentioning

confidence: 99%

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Human cerebrospinal fluid central memory CD4⁺T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin

Kivisäkk

Mahad²,

Callahan

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Cerebrospinal fluid (CSF) from healthy individuals contains between 1,000 and 3,000 leukocytes per ml. Little is known about trafficking patterns of leukocytes between the systemic circulation and the noninflamed CNS. In the current study, we characterized the surface phenotype of CSF cells and defined the expression of selected adhesion molecules on vasculature in the choroid plexus, the subarachnoid space surrounding the cerebral cortex, and the cerebral parenchyma. Using multicolor flow cytometry, we found that CSF cells predominantly consisted of CD4 ؉ ͞CD45RA ؊ ͞CD27 ؉ ͞ CD69 ؉ -activated central memory T cells expressing high levels of CCR7 and L-selectin. CD3 ؉ T cells were present in the choroid plexus stroma in autopsy CNS tissue sections from individuals who died without known neurological disorders. P-and E-selectin immunoreactivity was detected in large venules in the choroid plexus and subarachnoid space, but not in parenchymal microvessels. CD4 ؉ T cells in the CSF expressed high levels of P-selectin glycoprotein ligand 1, and a subpopulation of circulating CD4 ؉ T cells displayed P-selectin binding activity. Intercellular adhesion molecule 1, but not vascular cell adhesion molecule 1 or mucosal addressin cell adhesion molecule 1, was expressed in choroid plexus and subarachnoid space vessels. Based on these findings, we propose that T cells are recruited to the CSF through interactions between P-selectin͞P-selectin ligands and intercellular adhesion molecule 1͞lymphocyte function-associated antigen 1 in choroid plexus and subarachnoid space venules. These results support the overall hypothesis that activated memory T cells enter CSF directly from the systemic circulation and monitor the subarachnoid space, retaining the capacity to either initiate local immune reactions or return to secondary lymphoid organs. B etween 175,000 and 500,000 cells are present in the cerebrospinal fluid (CSF) of healthy individuals. Their functions and trafficking patterns are obscure, although it is believed that they participate in the immune defense of the CNS. Leukocytes traffic rapidly between blood and subarachnoid space (SAS), as indicated by studies in patients treated with anti-CD2 Abs, which demonstrated Ab-labeled cells in the CSF 18 h after infusion (1). The cellular composition of CSF, characterized by a predominance of lymphocytes but few erythrocytes, mononuclear phagocytes, or polymorphonuclear neutrophils, is not a simple reflection of peripheral blood (PB), suggesting a stringently regulated control over cell migration into the SAS.Despite an extensive literature delineating the formation of the fluid component of CSF, the sites of entry and exit of leukocytes to the CSF are not well characterized. Based on results of studies conducted in rodents, it has been proposed that lymphocytes migrate into the brain and spinal cord through the blood-brain barrier surrounding deep parenchymal vessels and subsequently drain into the CSF (2). This concept was challenged by a recent study using intravital microsco...

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“…4I). In addition, a fraction of parenchymal microvessels in histologically normal brains was ICAM-1 positive as reported (18).…”

Section: Icam-1 Expression On Cns Endothelial Cellssupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Human cerebrospinal fluid central memory CD4⁺T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin

Kivisäkk

Mahad²,

Callahan

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

508

408

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“…These data suggest that TG2 expressed by microglial cells in active grey matter lesions is probably not implicated in immune cell infiltration or migration. Of interest is that integrin expression has been demonstrated on microglial cells in MS lesions [86], and subsequent in vitro studies revealed a role for β 1 -integrin in microglial cell proliferation [87]. Indeed, in MS lesions, microglial and monocyte proliferation have been observed [88].…”

Section: Discussionmentioning

confidence: 99%

Tissue Transglutaminase in Marmoset Experimental Multiple Sclerosis: Discrepancy between White and Grey Matter

et al. 2014

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Infiltration of leukocytes is a major pathological event in white matter lesion formation in the brain of multiple sclerosis (MS) patients. In grey matter lesions, less infiltration of these cells occur, but microglial activation is present. Thus far, the interaction of β-integrins with extracellular matrix proteins, e.g. fibronectin, is considered to be of importance for the influx of immune cells. Recent in vitro studies indicate a possible role for the enzyme tissue Transglutaminase (TG2) in mediating cell adhesion and migration. In the present study we questioned whether TG2 is present in white and grey matter lesions observed in the marmoset model for MS. To this end, immunohistochemical studies were performed. We observed that TG2, expressed by infiltrating monocytes in white matter lesions co-expressed β1-integrin and is located in close apposition to deposited fibronectin. These data suggest an important role for TG2 in the adhesion and migration of infiltrating monocytes during white matter lesion formation. Moreover, in grey matter lesions, TG2 is mainly present in microglial cells together with some β1-integrin, whereas fibronectin is absent in these lesions. These data imply an alternative role for microglial-derived TG2 in grey matter lesions, e.g. cell proliferation. Further research should clarify the functional role of TG2 in monocytes or microglial cells in MS lesion formation.

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“…We also noticed that patients with clinical signs of active disease were those showing increased levels of circulating soluble adhesion molecules and sTNF-R1. Soluble forms of TNFα-R1 seems to prolong the half-life of the cytokine by protecting the biological activity against proteolytic degradation 2,6,7 and ultimately influencing neuroprotective or neurotoxic effects 2 with consequent death or survival of oligodendrocytes and myelin damage.…”

Section: Discussionmentioning

confidence: 99%

“…Such events depend upon sequential expression of different families of ligands (adhesion molecules: ICAM, VCAM, PECAM) and corresponding receptors (e.g. integrins: LFA-1; CD11a/CD18) influenced by locally produced cytokines [5][6][7] . A circulating soluble form of ICAM (sICAM-1) released mainly by CNS microvascular endothelial cells, has been detected in the serum of normal individuals 8 although high levels have been associated with pathological conditions [9][10][11] .…”

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confidence: 99%

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

Alves-Leon

Batista²,

Papais-Alvarenga

et al. 2001

Arq. Neuro-Psiquiatr.

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Cytokines and adhesion molecules have been implicated in the pathogenesis of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. In this study we analyzed intrathecal (CSF) and serum levels of soluble intercellular adhesion molecule (ICAM-1) and TNFalphaR (60kD) from 20 patients with clinically definite MS during acute relapse or stable disease. Comparing to control groups of healthy individuals and patients with intervertebral herniated disc, MS patients showed increased levels (p< 0.001) of sICAM-1 and TNFalphaR in both serum and CSF samples. Regardless stage of disease there was no significant difference in the levels of sICAM-1 during acute relapse (657±124.9 ng/ml) or remission (627±36.2 ng/ml). A steady increase of TNFalphaR (60kD) in both serum and CSF, indicate the existence of a continuous inflammatory process within the brain tissue of MS patients despite absence of clinical signs of disease activity.

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Distribution of Immunoglobulin Superfamily Members ICAM-1, -2, -3, and the β2 Integrin LFA-1 in Multiple Sclerosis Lesions

Cited by 15 publications

References 0 publications

Human cerebrospinal fluid central memory CD4⁺T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin

Human cerebrospinal fluid central memory CD4⁺T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin

Tissue Transglutaminase in Marmoset Experimental Multiple Sclerosis: Discrepancy between White and Grey Matter

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

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Distribution of Immunoglobulin Superfamily Members ICAM-1, -2, -3, and the β2 Integrin LFA-1 in Multiple Sclerosis Lesions

Cited by 15 publications

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Human cerebrospinal fluid central memory CD4+T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin

Human cerebrospinal fluid central memory CD4+T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin

Tissue Transglutaminase in Marmoset Experimental Multiple Sclerosis: Discrepancy between White and Grey Matter

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

Contact Info

Product

Resources

About

Human cerebrospinal fluid central memory CD4⁺T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin

Human cerebrospinal fluid central memory CD4⁺T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin