Identification of an inducible endothelial-leukocyte adhesion molecule.

Bevilacqua, Michael P.; Pober, Jordan S.; Mendrick, Donna L.; Cotran, Ramzi S.; Gimbrone, Michael A.

doi:10.1073/pnas.84.24.9238

Cited by 1,395 publications

(653 citation statements)

References 21 publications

(12 reference statements)

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“…In addition, TNF does not induce Pselectin transcription in humans [45], suggesting that the two molecules may not be co-expressed. E-selectin is a potential candidate for co-operation with fractalkine beecause its expression is induced by TNF or IL-1 [46]. Lim et.…”

Section: Discussionmentioning

confidence: 99%

Human fractalkine mediates leukocyte adhesion but not capture under physiological shear conditions; a mechanism for selective monocyte recruitment

et al. 2003

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Fractalkine is a unique chemokine possessing a long mucin-like stalk and a transmembrane region that has been proposed to act as an adhesion molecule. We investigated the ability of fractalkine to recruit leukocytes from whole blood, using an immobilized fractalkine fusion protein in the parallel-plate flow-chamber assay. Significant adhesion of leukocytes to fractalkine peaked at 2 dynes/cm 2 but was minimal at 10 dynes/cm 2 . In contrast, VCAM-1 could recruit cells from whole blood at 10 dynes/cm 2 . Co-immobilization of fractalkine and VCAM-1 at 10 dynes/cm 2 resulted in a twofold increase in adherent cells compared with VCAM-1 alone, suggesting that fractalkine can mediate adhesion at high shear if combined with a molecule that can mediate leukocyte tethering. Pretreatment of blood with pertussis toxin eliminated this increase in adhesion, implicating intracellular signaling in fractalkinemediated mechanisms of adhesion to co-immobilized fractalkine/VCAM-1. Analysis of the cell types recruited to fractalkine alone at low shear, or to fractalkine and VCAM-1 at 10 dynes/cm 2 , revealed that monocytes were recruited to fractalkine with the highest specificity. In conclusion, fractalkine is unlikely to act alone at shear forces found in most vascular beds where it most likely co-operates with tethering molecules, e.g. VCAM-1, in the recruitment of monocytes.

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Section: Discussionmentioning

confidence: 99%

Human fractalkine mediates leukocyte adhesion but not capture under physiological shear conditions; a mechanism for selective monocyte recruitment

et al. 2003

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“…The number of VCAM-1-expressing lung endothelial cells is increased in Aire -/-mice VCAM-1 was originally discovered in endothelial cells [42], where it is rapidly up-regulated in the presence of cytokines such as TNF-a, IL-1, IFN-c and IL-4 [43][44][45][46]. To assess whether the differential expression of VCAM was also present in Aire -/-endothelial cells, we purified mouse lung endothelial cells (MLEC) from Aire -/-and Aire +/+ mice and stimulated them for 16 h with increasing concentrations of IL-4.…”

Section: Blood Monocytes In Aps I Patients Are Increased and Display mentioning

confidence: 99%

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

et al. 2006

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Patients with autoimmune polyendocrine syndrome type I (APS I)suffer from endocrine and non-endocrine disorders due to mutations in the autoimmune regulator gene (AIRE). Mouse Aire is expressed both in thymic medullary epithelial cells and in peripheral antigen-presenting cells, suggesting a role in both central and peripheral tolerance. We here report that Aire -/-dendritic cells (DC) activate naive T cells more efficiently than do Aire +/+ DC. Expression array analyses of Aire -/-DC revealed differential regulation of 68 transcripts, among which, the vascular cell adhesion molecule-1 (VCAM-1) transcript was up-regulated in Aire -/-DC. Concurrently, the expression of the VCAM-1 protein was up-regulated on both Aire -/-DC and monocytes from APS I patients. Blocking the interaction of VCAM-1 prevented enhanced Aire -/-DC stimulation of T cell hybridomas. We determined an increased number of DC in spleen and lymph nodes and of monocytes in the blood from Aire -/-mice, and an increased number of blood monocytes in APS I patients. Our findings imply a role for Aire in peripheral DC regulation of T cell activation, and suggest that Aire participates in peripheral tolerance.Supporting information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2006/35240_s.pdf IntroductionInactivation of the autoimmune regulator gene (AIRE) [1][2][3] causes autoimmunity in patients with autoimmune polyendocrine syndrome type I (APS I, APECED, OMIM 240300) and in a gene targeted mouse model [4,5]. APS I is a rare monogenic autosomal recessive disease without HLA association [6,7], which is prevalent in isolated populations [8][9][10]. APS I patients develop a progressive loss of tolerance against self antigens and suffer from multiorgan failures due to the immunological destruction of adrenals, parathyroid glands and b cells of the islets of Langerhans [11]. Many of the APS I organ-specific autoantigens have been identified and characterized [12,13]. In addition, as a sign of immune dysfunction, these patients have difficulties clearing Candida albicans infections in mucosal membranes [14]. Functional studies of AIRE suggest a role as a transcription factor and in vitro transactivating studies support this notion [15][16][17][18]. Moreover, the PHD1 domain of AIRE has been suggested to have an E3 ubiquitin ligase activity in cell-free assays [19], findings in variance with a recent report [20]. Aire is highly expressed in a subset of the medullary thymic epithelial cells (mTEC) as well as in DC in the spleen and lymph nodes [21][22][23][24], indicating a potential role in immunological tolerance.To characterize the function of Aire, we previously engineered an Aire-deficient mouse targeting the most common APS I mutation [4]. Aire-deficient mice develop multiple organ-specific autoantibodies and lymphocytic infiltrates, thus mimicking some of the features of human APS I [4]. Subsequently, the role of Aire in negative selection was demonstrated [5]. These findings were further supported using TCR transgenic mic...

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“…1011 Tu mor necrosis factor-α and IL-lß were also found to induce and increase the expression of adhesion receptors on the membrane of endothelial cells and integrins on PMN that are reciprocally involved in intracellular adhesion. 12 …”

Section: Nflammatory Cytokines Suchmentioning

confidence: 99%

Enhanced Release of Elastase Is Not Concomitant With Increased Secretion of Granulocyte-Activating Cytokines in Whole Blood From Patients With Sepsis

Ertel

Jarrar²,

Jochum³

et al. 1994

Arch Surg

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Identification of an inducible endothelial-leukocyte adhesion molecule.

Cited by 1,395 publications

References 21 publications

Human fractalkine mediates leukocyte adhesion but not capture under physiological shear conditions; a mechanism for selective monocyte recruitment

Human fractalkine mediates leukocyte adhesion but not capture under physiological shear conditions; a mechanism for selective monocyte recruitment

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

Enhanced Release of Elastase Is Not Concomitant With Increased Secretion of Granulocyte-Activating Cytokines in Whole Blood From Patients With Sepsis

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