Cytokine-regulated adhesion between encephalitogenic T lymphocytes and cerebrovascular endothelial cells

McCarron, Richard M.; Wang, L.; Racke, Michael K.; McFarlin, Dale E.; Spatz, Maria

doi:10.1016/0165-5728(93)90071-6

Cited by 122 publications

(35 citation statements)

References 42 publications

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“…Stimulation of HUVEC with cytokines increases their adherence for leucocytes [15], and this also occurs with cerebral endothelial cells derived from the rat [16], mouse [17] and man [18]. When rodent cerebral microvessels in culture are cytokine-activated [19], their maximal expression of E-selectin is maintained for a longer period (24-48 h) than on monolayers of HUVEC (maximal expression 4-6 h).…”

Section: Discussionmentioning

confidence: 99%

Enhanced binding of lymphocytes from patients with multiple sclerosis to tumour necrosis factor-alpha (TNF-α)-treated endothelial monolayers: associations with clinical relapse and adhesion molecule expression

Vora

Perkin

McCoy

et al. 1996

Clinical and Experimental Immunology

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SUMMARYThis study investigated the adherent properties and adhesion molecule expression of blood mononuclear cells (MNC) from a total of 84 patients with multiple sclerosis (MS). The MNC from MS patients were significantly more adherent than cells from normal healthy subjects to endothelial monolayers pretreated with 0 . 01 U/ml TNF-® (103% increase; P 0 . 002), 0 . 1 U/ml TNF-® (80% increase; P < 0 . 01) and 1 . 0 U/ml TNF-® (41% increase; P < 0 . 02), and to endothelium pretreated with 10 U/ml IL-1¯(44% increase; P < 0 . 05) and 100 U/ml interferon-gamma (IFN-°) (100% increase; P < 0 . 05). This augmented adhesion was a property of the lymphocytes, in particular CD4 + cells, and was inversely related to the time of onset of clinical relapse. The percentage of lymphocytes bearing the adhesion molecules CD49d, CD29 and CD62L was increased in MS blood, but the level of CD29 and CD62L expression was reduced. We infer that circulating lymphocytes in MS are predisposed to cross endothelial barriers at sites where inflammation has already commenced.

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Section: Discussionmentioning

confidence: 99%

Enhanced binding of lymphocytes from patients with multiple sclerosis to tumour necrosis factor-alpha (TNF-α)-treated endothelial monolayers: associations with clinical relapse and adhesion molecule expression

Vora

Perkin

McCoy

et al. 1996

Clinical and Experimental Immunology

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“…[37][38][39] Both proinflammatory cytokines lead to an increased adherence and transmigration of encephalitogenic T cells into the CNS. 40,41 Once in the CNS, those T cells that recognize a CNS antigen, in our case MOG, will persist, recruit other inflammatory cells, and initiate the formation of an inflammatory, demyelinating CNS lesion. 42 The combination of a subclinical immune response against MOG and the localized stereotactic injection of proinflammatory cytokines into the thoracic spinal cord led to the formation of a focal inflammatory demyelinating lesion.…”

Section: Discussionmentioning

confidence: 99%

Targeting Experimental Autoimmune Encephalomyelitis Lesions to a Predetermined Axonal Tract System Allows for Refined Behavioral Testing in an Animal Model of Multiple Sclerosis

Kerschensteiner

Stadelmann

Buddeberg

et al. 2004

The American Journal of Pathology

105

103

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In multiple sclerosis (MS) the structural damage to axons determines the persistent clinical deficit patients acquire during the course of the disease. It is therefore important to test therapeutic strategies that can prevent or reverse this structural damage. The conventional animal model of MS, experimental autoimmune encephalomyelitis (EAE), typically shows disseminated inflammation in the central nervous system, which leads to a clinical deficit that cannot be directly attributed to a defined tract system. For this reason we have developed a localized EAE model, in which large inflammatory lesions are targeted to the dorsal columns of the spinal cord, an area including the corticospinal tract. These lesions show the pathological hallmarks of MS plaques and lead to reproducible and pronounced deficits in hindlimb locomotion. Because of the anatomical specificity of this technique we can now use highly sensitive behavioral tests that assess the functional integrity of specific axonal tracts. We show that these tests are predictive of the site and extent of a given lesion and are more sensitive for assessing the clinical course than the scales commonly used for disseminated EAE models. We believe that this targeted EAE model will become a Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS).1 Our understanding of the mechanisms that underlie MS has progressed significantly throughout the last years, yet our means for therapeutic intervention are still very limited. It is believed that in MS an autoimmune dysregulation leads to an inflammatory attack on the resident cells of the CNS.1 Recent studies have emphasized that the target of this inflammatory attack is not the myelin sheath alone but rather the entire myelin-axonal unit.2,3 Neuropathological studies have provided evidence that acute structural damage to axons is a prominent feature of MS lesions starting from the very early stages of the disease. 4 -6 The clinical importance of the structural axon damage is further underlined by the close correlation between neuroradiological markers of axon damage and the persistent neurological deficit in a given MS patient. 7,8 It is thus of central importance to develop therapeutic strategies that can prevent or repair axonal damage in MS. The basis for the development and evaluation of such strategies is the availability of suitable animal models, which should both reflect the pathological hallmarks of MS and allow for the quantification of therapeutic effects on axonal damage and repair.

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“…Also, TGF-/31 has been demonstrated to have a protective effect in several T cell-mediated disease models including Borna disease, experimental allergic encephalomyelitis (an experimental model for human multiple sclerosis), and T cell-mediated arthritis (70)(71)(72)(73). As with the reperfusion injury and meningitis models, the protective effect of TGF-f3 in these T cell-mediated disease models may also be related, in part, to the inhibitory effect of TGF-f3 on the adhesiveness of endothelial cells for neutrophils and T lymphocytes (60)(61)(62). In light of these in vitro and in vivo effects of TGF-f, on the endothelium, it has been suggested by Gamble and Vadas (60) that maintenance of the nonadhesiveness of endothelial cells is an active phenomenon mediated by circulating TGF- Two mouse models also support the conclusion that the endothelium is a major target for circulating TGF-16 in vivo.…”

Section: Methodsmentioning

confidence: 99%

“…Observed responses of endothelial cell behavior include growth inhibition and induction of tubelike structures (53)(54)(55)(56), stimulation of angiogenesis (57), induction of endothelin expression (58), a decrease in the surface density of fenestrae (59), and an inhibition of the adhesiveness of endothelial cells for neutrophils and T lymphocytes (60)(61)(62) due to a decreased synthesis of endothelial E-selectin (63). The effect of systemic TGF-,61 on the endothelium in vivo is less well understood.…”

Section: Methodsmentioning

confidence: 99%

Specific binding of endocrine transforming growth factor-beta 1 to vascular endothelium.

Dickson¹,

Philip²,

Warshawsky³

et al. 1995

J. Clin. Invest.

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Cytokine-regulated adhesion between encephalitogenic T lymphocytes and cerebrovascular endothelial cells

Cited by 122 publications

References 42 publications

Enhanced binding of lymphocytes from patients with multiple sclerosis to tumour necrosis factor-alpha (TNF-α)-treated endothelial monolayers: associations with clinical relapse and adhesion molecule expression

Enhanced binding of lymphocytes from patients with multiple sclerosis to tumour necrosis factor-alpha (TNF-α)-treated endothelial monolayers: associations with clinical relapse and adhesion molecule expression

Targeting Experimental Autoimmune Encephalomyelitis Lesions to a Predetermined Axonal Tract System Allows for Refined Behavioral Testing in an Animal Model of Multiple Sclerosis

Specific binding of endocrine transforming growth factor-beta 1 to vascular endothelium.

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