Differential Leukocyte Recruitment From Whole Blood Via Endothelial Adhesion Molecules Under Shear Conditions

Blood ◽  
1998 ◽  
Vol 92 (12) ◽  
pp. 4691-4699 ◽  
Author(s):  
Paul H. Reinhardt ◽  
Paul Kubes
Keyword(s):  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Whole Blood ◽  
Mononuclear Cells ◽  
The Novel ◽  
Vascular Cell Adhesion ◽  
High Affinity ◽  
Relative Shear ◽  
Endothelial Adhesion Molecules ◽  
Molecule Concentration

The objective of this study was to determine if vascular cell adhesion molecule (VCAM-1), E-selectin, and P-selectin could selectively recruit leukocyte subpopulations, and whether this was affected by shear force or adhesion molecule concentration. Cover slips coated with purified adhesion molecules were incorporated into laminar flow chambers. Whole human blood was perfused for 5 minutes over these cover slips at relative shear forces of 2 to 40 dynes/cm2. Chasing the whole blood with buffer permitted visualization of leukocyte-substratum interactions. Leukocytes were observed to roll on and adhere to VCAM-1 at shears between 2 and 15 dynes/cm2. As assessed by cover slip staining, the majority of these cells were lymphocytes, but eosinophils, monocytes, and, surprisingly, neutrophils were also recruited, events inhibitable by anti–4-integrin antibody (HP1/2). Neutrophils were effectively recruited onto the selectins, with interactions occurring at shears as high as 30 and 40 dynes/cm2 for E- and P-selectin respectively. Eosinophils had high affinity for P- but not E-selectin. Mononuclear cells did not have high affinity for either selectin, but interacted avidly with VCAM-1. Antibodies against P-selectin (G1) and E-selectin (ES-1) completely blocked interactions on these substrates. Reducing the concentration of adhesion molecules did not appreciably change recruitment patterns except for VCAM-1, where neutrophils were no longer recruited. The novel use of whole blood in flow chambers shows a partial selectivity of selectins and VCAM-1 for certain subpopulations of leukocytes under varying physiologic shear conditions.

Differential Leukocyte Recruitment From Whole Blood Via Endothelial Adhesion Molecules Under Shear Conditions

Blood ◽  
1998 ◽  
Vol 92 (12) ◽  
pp. 4691-4699 ◽  
Author(s):  
Paul H. Reinhardt ◽  
Paul Kubes
Keyword(s):  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Whole Blood ◽  
Mononuclear Cells ◽  
The Novel ◽  
Vascular Cell Adhesion ◽  
High Affinity ◽  
Relative Shear ◽  
Endothelial Adhesion Molecules ◽  
Molecule Concentration

Abstract The objective of this study was to determine if vascular cell adhesion molecule (VCAM-1), E-selectin, and P-selectin could selectively recruit leukocyte subpopulations, and whether this was affected by shear force or adhesion molecule concentration. Cover slips coated with purified adhesion molecules were incorporated into laminar flow chambers. Whole human blood was perfused for 5 minutes over these cover slips at relative shear forces of 2 to 40 dynes/cm2. Chasing the whole blood with buffer permitted visualization of leukocyte-substratum interactions. Leukocytes were observed to roll on and adhere to VCAM-1 at shears between 2 and 15 dynes/cm2. As assessed by cover slip staining, the majority of these cells were lymphocytes, but eosinophils, monocytes, and, surprisingly, neutrophils were also recruited, events inhibitable by anti–4-integrin antibody (HP1/2). Neutrophils were effectively recruited onto the selectins, with interactions occurring at shears as high as 30 and 40 dynes/cm2 for E- and P-selectin respectively. Eosinophils had high affinity for P- but not E-selectin. Mononuclear cells did not have high affinity for either selectin, but interacted avidly with VCAM-1. Antibodies against P-selectin (G1) and E-selectin (ES-1) completely blocked interactions on these substrates. Reducing the concentration of adhesion molecules did not appreciably change recruitment patterns except for VCAM-1, where neutrophils were no longer recruited. The novel use of whole blood in flow chambers shows a partial selectivity of selectins and VCAM-1 for certain subpopulations of leukocytes under varying physiologic shear conditions.

Expression of Endothelial Adhesion Molecules After Radiosurgery in an Animal Model of Arteriovenous Malformation

Neurosurgery ◽  
2010 ◽  
Vol 67 (4) ◽  
pp. 976-983 ◽  
Author(s):  
Kingsley P Storer ◽  
Jian Tu ◽  
Marcus A Stoodley ◽  
Robert I Smee
Keyword(s):  
Animal Model ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Endothelial Adhesion Molecules ◽  
Cell Adhesion Molecule 1

Abstract BACKGROUND: Endothelial adhesion molecules may be important in the response of brain arteriovenous malformations (AVMs) to radiosurgery. In addition to a putative role in the occlusive process after radiosurgery, they may serve as potential targets for biological strategies to accelerate intravascular thrombosis. OBJECTIVE: To determine the temporal expression of E-selectin and vascular cell adhesion molecule-1 in an animal model of AVMs. METHODS: Forty-one Sprague-Dawley rats underwent surgical creation of a carotid-to-jugular anastomosis. Radiosurgery (25 Gy) was delivered to the model “nidus” after 6 weeks, and the tissue was harvested 1 to 84 days after radiosurgery. Control groups received sham irradiation. Immunofluorescence was used to study the expression of E-selectin and vascular cell adhesion molecule-1. RESULTS: Endothelial E-selectin expression was limited to regions receiving radiosurgery. E-selectin expression reached maximal expression at 24 hours after radiosurgery and was sustained for another 24 hours before gradually reducing to baseline at 84 days post-radiosurgery (P < .01). Vascular cell adhesion molecule-1 expression remained at the baseline level for the first week; a 50% increase was observed at 21 days after radiosurgery, which was sustained for another 3 weeks before returning to the baseline at 84 days after radiosurgery (P < .05). CONCLUSION: Radiosurgery stimulates early expression of E-selectin and delayed up-regulation of vascular cell adhesion molecule-1 on the endothelial surface of the AVM model nidus. Cell adhesion molecule expression may play an important role in the process leading to vascular obliteration after irradiation. These molecular alterations may be harnessed to promote thrombosis in the irradiated vasculature using a vascular targeting agent.

Various adhesion molecules impair microvascular leukocyte kinetics in ventilator-induced lung injury

2006 ◽  
Vol 290 (6) ◽  
pp. L1059-L1068 ◽  
Author(s):  
Naoki Miyao ◽  
Yukio Suzuki ◽  
Kei Takeshita ◽  
Hiroyasu Kudo ◽  
Makoto Ishii ◽  
...  
Keyword(s):  
Lung Injury ◽  
Fluorescence Microscopy ◽  
Adhesion Molecules ◽  
Mononuclear Cells ◽  
Tissue Injury ◽  
Laser Fluorescence ◽  
Confocal Laser ◽  
Polymorphonuclear Cells ◽  
Ventilator Induced Lung Injury ◽  
Endothelial Adhesion Molecules

Although the endothelial expression of various adhesion molecules substantially differs between pulmonary microvessels, their importance for neutrophil and lymphocyte sequestration in ventilator-induced lung injury (VILI) has not been systematically analyzed. We investigated the kinetics of polymorphonuclear cells (PMN) and mononuclear cells (MN) in the acinar microcirculation of the isolated rat lung with VILI by real-time confocal laser fluorescence microscopy, with or without inhibition of ICAM-1, VCAM-1, or P-selectin by monoclonal antibodies (MAb). Adhesion molecules in each microvessel were estimated by intravital fluorescence microscopy or immunohistochemical staining. In high tidal volume-ventilated lungs, 1) ICAM-1, VCAM-1, and P-selectin were differently upregulated in venules, arterioles, and capillaries; 2) venular PMN rolling was improved by inhibition of ICAM-1, VCAM-1, or P-selectin, whereas arteriolar PMN rolling was improved by ICAM-1 or VCAM-1 inhibition; 3) capillary PMN entrapment was ameliorated only by anti-ICAM-1 MAb; and 4) MN rolling in venules and arterioles and MN entrapment in capillaries were improved by ICAM-1 and VCAM-1 inhibition. In conclusion, the contribution of endothelial adhesion molecules to abnormal leukocyte behavior in VILI-injured microcirculation is microvessel and leukocyte specific. ICAM-1- and VCAM-1-dependent, but P-selectin-independent, arteriolar PMN rolling, which is expected to reflect the initial stage of tissue injury, should be taken as a phenomenon unique to ventilator-associated lung injury.

TNF-α-induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent

2003 ◽  
Vol 284 (2) ◽  
pp. C422-C428 ◽  
Author(s):  
Makoto Sasaki ◽  
D. Ostanin ◽  
J. W. Elrod ◽  
T. Oshima ◽  
P. Jordan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Nadph Oxidase ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Tnf Α ◽  
Oxidase Inhibition ◽  
Endothelial Adhesion Molecules ◽  
Cytochrome P 450

It is strongly suspected that cytokine-induced gene expression in inflammation is oxidant mediated; however, the intracellular sources of signaling oxidants remain controversial. In inflammatory bowel disease (IBD) proinflammatory cytokines, such as TNF-α, trigger gene expression of endothelial adhesion molecules including mucosal addressin cell adhesion molecule-1 (MAdCAM-1). MAdCAM-1 plays an essential role in gut inflammation by governing the infiltration of leukocytes into the intestine. Several groups suggest that endothelial-derived reduced NADP (NADPH) oxidase produces signaling oxidants that control the expression of adhesion molecules (E-selectin, ICAM-1, VCAM-1). In addition to NADPH oxidase, cytochrome P-450 (CYP450) monooxygenases have also been shown to trigger cytokine responses. We found that in high endothelial venular cells (SVEC4-10), multiple inhibitors of CYP450 monooxygenases (SKF-525a, ketoconazole, troleandomycin, itraconazole) attenuated TNF-α induction of MAdCAM-1, whereas NADPH oxidase inhibition (PR-39) did not. Conversely, E-selectin, ICAM-1, and VCAM-1 induction requires both NADPH oxidase and CYP450-derived oxidants. We show here that MAdCAM-1 induction may depend exclusively on CYP450-derived oxidants, suggesting that CYP450 blockers might represent a possible novel therapeutic treatment for human IBD.

scholarly journals Selective Upregulation of Endothelial E-Selectin in Response to Helicobacter pylori-Induced Gastritis

2009 ◽  
Vol 77 (7) ◽  
pp. 3109-3116 ◽  
Author(s):  
Helena Svensson ◽  
Malin Hansson ◽  
Jan Kilhamn ◽  
Steffen Backert ◽  
Marianne Quiding-Järbrink
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Adhesion Protein ◽  
Type Iv ◽  
Endothelial Adhesion Molecules ◽  
H Pylori ◽  
Vascular Adhesion

ABSTRACT Helicobacter pylori is one of the most common bacterial pathogens, infecting up to 50% of the world's population. The host is not able to clear the infection, leading to life-long chronic inflammation with continuous infiltration of lymphocytes and granulocytes. The migration of leukocytes from the blood into inflamed tissue is dependent on adhesion molecules expressed on the vascular endothelium. The aim of this study was to characterize the effect of H. pylori-induced gastritis with regard to the expression of endothelial adhesion molecules in the gastric mucosa and compare this to other types of chronic mucosal inflammations. Our results demonstrate an increased level of expression of the adhesion molecule E-selectin, but not of intracellular adhesion molecule 1, vascular adhesion molecule 1, or vascular adhesion protein 1, in H. pylori-induced gastritis but not in gastritis induced by acetylsalicylic acid or pouchitis. The upregulated E-selectin expression was determined to be localized to the gastric mucosa rather than being a systemic response to the infection. Moreover, the H. pylori type IV secretion system encoded by the cag pathogenicity island (cagPAI) was found to be an important determinant for the upregulation of human endothelial E-selectin expression in vitro, and this process is probably dependent on the CagL protein, mediating binding to α5β1 integrins. Thus, endothelial E-selectin expression induced by H. pylori probably contributes to the large influx of neutrophils and macrophages seen in infected individuals, and our results suggest that this process may be more pronounced in patients infected with cagPAI-positive H. pylori strains and may thereby contribute to tissue damage in these individuals.

scholarly journals Migration inhibitory factor up-regulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 via Src, PI3 kinase, and NFκB

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2252-2261 ◽  
Author(s):  
M. Asif Amin ◽  
Christian S. Haas ◽  
Kui Zhu ◽  
Pamela J. Mansfield ◽  
Michael J. Kim ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Cell Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
Vascular Cell Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Adhesion Molecule 1

AbstractCell adhesion molecules are critical in monocyte (MN) recruitment in immune-mediated and hematologic diseases. We investigated the novel role of recombinant human migration inhibitory factor (rhMIF) in up-regulating vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and their signaling pathways in human MNs. rhMIF-induced expression of VCAM-1 and ICAM-1 was significantly higher compared with nonstimulated MNs. rhMIF induced MN VCAM-1 and ICAM-1 expression in a concentration-dependent manner (P < .05). Antisense oligodeoxynucleotides (ODNs) and inhibitors of Src, PI3K, p38, and NFκB significantly reduced rhMIF-induced MN VCAM-1 and ICAM-1 expression (P < .05). However, Erk1/2 and Jak2 were not involved. Silencing RNA directed against MIF, and inhibitors of Src, PI3K, NFκB, anti–VCAM-1, and anti–ICAM-1 significantly inhibited rhMIF-induced adhesion of HL-60 cells to human dermal microvascular endothelial cells (HMVECs) or an endothelial cell line, HMEC-1, in cell adhesion assays, suggesting the functional significance of MIF-induced adhesion molecules (P < .05). rhMIF also activated MN phospho-Src, -Akt, and -NFκB in a time-dependent manner. rhMIF induced VCAM-1 and ICAM-1 up-regulation in 12 hours via Src, PI3K, and NFκB as shown by Western blotting and immunofluorescence. MIF and MIF-dependent signaling pathways may be a potential target for treating diseases characterized by up-regulation of cell adhesion molecules.

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