Adhesion of Monocytes to Vascular Cell Adhesion Molecule-1–Transduced Human Endothelial Cells

Gerszten, Robert E.; Lim, Yong Ching; Ding, Han; Snapp, Karen R.; Kansas, Geoffrey S.; Dichek, David A.; Cabañas, Carlos; Sánchez‐Madrid, Francisco; Gimbrone, Michael A.; Rosenzweig, Anthony; Luscinskas, Francis W.

doi:10.1161/01.res.82.8.871

Cited by 104 publications

(58 citation statements)

References 31 publications

(41 reference statements)

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“…Both bloodborn macrophages and reactive microglia are ED1-positive. Vascular cell adhesion molecule-1 was reported to be more effective at mediating the initial attachment of monocytes than of lymphocytes, and to be sufficient to initiate events culminating in monocyte, but not lymphocyte, transmigration (Gerszten et al, 1998). Also, VCAM-1 supports monocyte adhesion to endothelial cells better than ICAM-1 and selectins (Zhang et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Anti-VCAM-1 Antibodies did not Protect against Ischemic Damage Either in Rats Or in Mice

Justicia

Martín

Rojas

et al. 2006

J Cereb Blood Flow Metab

100

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Cerebral ischemia triggers an inflammatory process involving the infiltration of leukocytes to the parenchyma. Circulating leukocytes adhere to the vascular wall through adhesion molecules. Here we quantified the in vivo expression of vascular cell adhesion molecule-1 (VCAM-1) in the brain, heart and lungs from 6 to 48 h after transient middle cerebral artery (MCA) occlusion in rats, by intravenous injection of a tracer radiolabelled anti-VCAM-1 antibody. The vascular localization of VCAM-1 was verified by immunohistochemistry after in vivo injection of the antibody. Vascular cell adhesion molecule-1 was strongly induced (4-fold at 24 h) in the microvasculature of the ischemic area, and, to a lesser extent, in the contralateral hemisphere and in a remote organ, the heart, but not in the lungs, indicating that the inflammatory process propagates beyond the injured brain. We injected intravenously either blocking doses of anti-VCAM-1 antibodies or control antibodies after MCA occlusion in rats and mice. We evaluated the neurological score in rats, and infarct volume at 2 days in rats and at 4 days in mice. Anti-VCAM-1 did not protect against ischemic damage either in rats or in mice. Vascular cell adhesion molecule-1 blockade significantly decreased the number of ED1 (labeling monocytes /macrophages/reactive microglia)-positive cells in the ischemic rat brain. However, it did not reduce the numbers of infiltrating neutrophils and lymphocytes, and total leukocytes (CD45 positive), which showed a trend to increase. The results show vascular upregulation of VCAM-1 after transient focal ischemia, but no benefits of blocking VCAM-1, suggesting that this is not a therapeutical strategy for stroke treatment.

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Section: Discussionmentioning

confidence: 99%

Anti-VCAM-1 Antibodies did not Protect against Ischemic Damage Either in Rats Or in Mice

Justicia

Martín

Rojas

et al. 2006

J Cereb Blood Flow Metab

100

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“…However, under low-flow conditions, the interaction of VCAM-1 with the VLA4 integrin can mediate rolling and adhesion of monocytes without the need for selectins or ␤2 integrins (32)(33)(34). The VLA4/VCAM-1 interaction is less effective in supporting rolling and adhesion of lymphocytes 258 (35,36) and is completely incapable of supporting neutrophil adhesion because VLA4 is not present on neutrophils (27). These findings help to explain why monocytes/macrophages and, to a lesser extent, T cells adhere to the ductus endothelium after ductus closure (Figs.…”

Section: Discussionmentioning

confidence: 99%

The Role of Monocyte-Derived Cells and Inflammation in Baboon Ductus Arteriosus Remodeling

et al. 2005

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Inflammatory processes play a crucial role in the pathogenesis of atherosclerosis and other vascular disorders. We hypothesized that ischemia of the ductus arteriosus might initiate an active inflammatory response that could play a role in ductus remodeling and permanent closure. To test this hypothesis, we studied effects of postnatal ductus construction on inflammatory processes and remodeling in late-gestation fetal and newborn baboons, and preterm newborn baboons. After postnatal ductus constriction, the expression of several genes known to be essential for atherosclerotic remodeling [vascular cell adhesion molecule (VCAM)-1, E-selectin, IL-8, macrophage colony stimulating factor-1, CD154, interferon-␥, IL-6, and tumor necrosis factor-␣] was increased in the ductus wall. We were unable to detect intercellular adhesion molecule (ICAM)-1, ICAM-2, Pselectin, monocyte chemoattractant protein-1, or IL-1 by either real-time PCR or immunohistochemistry. VCAM-1, which is newly expressed by luminal cells of the closed ductus, is an important ligand for the mononuclear cell adhesion receptor VLA4. After postnatal constriction, VLA4 ϩ monocytes/ macrophages (CD68 ϩ and CD14 ϩ ) and, to a lesser extent, T-lymphocytes adhered to the ductus wall. Neutrophils and platelets were not observed. The extent of postnatal neointimal remodeling (both endothelial cell layering and subendothelial space thickening) was associated with the degree of mononuclear cell adhesion. Similarly, the extent of vasa vasorum ingrowth correlated with the invasion of CD68 ϩ cells, from the adventitia into the muscle media. Based on these data, we conclude that the inflammatory response following postnatal ductus constriction may be as necessary for ductus remodeling as it is for atherosclerotic remodeling. Closure of the full-term ductus arteriosus occurs in two phases. First, smooth muscle constriction obstructs the ductus' lumen. Then, anatomic remodeling permanently occludes the lumen. The initial constriction appears to be the required stimulus for anatomic closure. During constriction, loss of luminal and vasa vasorum flow produce a zone of ischemichypoxia in the ductus' muscle media that induces the following anatomic changes: luminal endothelial proliferation, subendothelial thickening, ingrowth of vasa vasorum, and cell death (1). The preterm newborn is capable of remodeling its ductus, just like the full-term newborn, if it can impede its luminal flow and develop the same degree of ischemic-hypoxia as found at term (2).Although the cell death and ingrowth of vasa vasorum in the ductus wall appear to be due to ATP depletion (3,4) and VEGF induction (5), respectively, the mechanism(s) responsible for the neointimal changes are still unknown. It is now clear that inflammatory processes play a crucial role in the pathogenesis of several vascular disorders (6 -9). The most studied model of

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“…ICAM-1/␤ 2 integrin interaction is a crucial event for neutrophil endothelial cell transmigration in vitro and neutrophil recruitment in vivo (68,69). On the contrary, IL-13 up-regulates the expression of VCAM-1, the counterreceptor of very late Ag-4, a ␤ 1 integrin expressed by monocytes and eosinophils and relevant for their interaction with cytokine-activated endothelium (67,70,71). IL-13 and IL-4 can act in synergism with TNF to promote the secretion of IL-8 by human endothelial cells (67,72,73).…”

Section: Discussionmentioning

confidence: 99%

Induction of Functional IL-8 Receptors by IL-4 and IL-13 in Human Monocytes

Bonecchi

Facchetti

Dusi

et al. 2000

The Journal of Immunology

123

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IL-8 and related Glu-Leu-Arg (ELR+) CXC chemokines are potent chemoattractants for neutrophils but not for monocytes. IL-13 and IL-4 strongly increased CXCR1 and CXCR2 chemokine receptor expression in human monocytes, macrophages, and dendritic cells. The effect was receptor- and cell type-selective, in that CCRs were not increased and no augmentation was seen in neutrophils. The effect was rapid, starting at 4 h, and concentration dependent (EC50 = 6.2 and 8.3 ng/ml for CXCR1 and CXCR2, respectively) and caused by new transcriptional activity. IL-13/IL-4-treated monocytes showed increased CXCR1 and CXCR2 membrane expression. IL-8 and related ELR+ chemokines were potent and effective chemotactic agents for IL-13/IL-4-treated monocytes, but not for untreated mononuclear phagocytes, with activity comparable to that of reference monocyte attractants, such as MCP-1. In the same cells, IL-8 also caused superoxide release. Macrophages and dendritic cells present in biopsies from Omenn’s syndrome and atopic dermatitis patients, two Th2 skewed pathologies, expressed IL-8 receptors by immunohistochemistry. These results show that IL-13 and IL-4 convert IL-8 and related ELR+ chemokines, prototypic neutrophil attractants, into monocyte chemotactic agonists, by up-regulating receptor expression. Therefore, IL-8 and related chemokines may contribute to the accumulation and positioning of mononuclear phagocytes in Th2-dominated responses.

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Adhesion of Monocytes to Vascular Cell Adhesion Molecule-1–Transduced Human Endothelial Cells

Cited by 104 publications

References 31 publications

Anti-VCAM-1 Antibodies did not Protect against Ischemic Damage Either in Rats Or in Mice

Anti-VCAM-1 Antibodies did not Protect against Ischemic Damage Either in Rats Or in Mice

The Role of Monocyte-Derived Cells and Inflammation in Baboon Ductus Arteriosus Remodeling

Induction of Functional IL-8 Receptors by IL-4 and IL-13 in Human Monocytes

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