scholarly journals L-Selectin Shedding Regulates Leukocyte Recruitment

2001 ◽  
Vol 193 (7) ◽  
pp. 863-872 ◽  
Author(s):  
Ali Hafezi-Moghadam ◽  
Kennard L. Thomas ◽  
Alyson J. Prorock ◽  
Yuqing Huo ◽  
Klaus Ley
Keyword(s):  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Leukocyte Rolling ◽  
Lymphocyte Function ◽  
Factor Α ◽  
Necrosis Factor ◽  
Dependent Mechanism

The physiologic role of L-selectin shedding is unknown. Here, we investigate the effect of L-selectin shedding on firm adhesion and transmigration. In a tumor necrosis factor α–induced model of inflammation, inhibition of L-selectin shedding significantly increased firm adhesion and transmigration by a lymphocyte function–associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1–dependent mechanism. We examined the quality of leukocyte rolling and L-selectin–mediated signaling. Blockade of L-selectin shedding significantly reduced the “jerkiness” of leukocyte rolling, defined as the variability of velocity over time. A low level of jerkiness was also observed in the rolling of microbeads conjugated with L-selectin, a model system lacking the mechanism for L-selectin shedding. Inhibition of L-selectin shedding potentiated activation of LFA-1 and Mac-1 induced by L-selectin cross-linking as shown by activation epitope expression and binding of ICAM-1–conjugated beads. We conclude that inhibition of L-selectin shedding increases leukocyte adhesion and transmigration by (a) increasing leukocyte exposure to the inflamed endothelium by decreasing jerkiness and (b) promoting leukocyte activation by outside-in signaling. These observations help to resolve the apparent discrepancy between the minor contribution of L-selectin to rolling and the significant leukocyte recruitment defect in L-selectin knockout mice.

scholarly journals Tumor necrosis factor α (TNF-α) receptor-II is required for TNF-α–induced leukocyte-endothelial interaction in vivo

Blood ◽  
2006 ◽  
Vol 109 (5) ◽  
pp. 1938-1944 ◽  
Author(s):  
Unni M. Chandrasekharan ◽  
Maria Siemionow ◽  
Murat Unsal ◽  
Lin Yang ◽  
Earl Poptic ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Leukocyte Adhesion ◽  
Leukocyte Rolling ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Leukocyte Adhesion Molecules

Abstract Tumor necrosis factor-α (TNF-α) binds to 2 distinct cell-surface receptors: TNF-α receptor-I (TNFR-I: p55) and TNF-α receptor-II (TNFR-II: p75). TNF-α induces leukocyte adhesion molecules on endothelial cells (ECs), which mediate 3 defined steps of the inflammatory response; namely, leukocyte rolling, firm adhesion, and transmigration. In this study, we have investigated the role of p75 in TNF-α–induced leukocyte adhesion molecules using cultured ECs derived from wild-type (WT), p75-null (p75−/−), or p55-null (p55−/−) mice. We observed that p75 was essential for TNF-α–induced E-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) expression. We also investigated the putative role of p75 in inflammation in vivo using an intravital microscopic approach with a mouse cremaster muscle model. TNF-α–stimulated leukocyte rolling, firm adhesion to ECs, and transmigration were dramatically reduced in p75−/− mice. Transplanted WT cremaster in p75−/− mice showed a robust leukocyte rolling and firm adhesion upon TNF-α activation, suggesting that the impairment in EC-leukocyte interaction in p75−/− mice is due to EC dysfunction. These results demonstrate, for the first time, that endothelial p75 is essential for TNF-α–induced leukocyte–endothelial-cell interaction. Our findings may contribute to the identification of novel p75-targeted therapeutic approaches for inflammatory diseases.

Selectin-independent leukocyte rolling and adhesion in mice deficient in E-, P-, and L-selectin and ICAM-1

2001 ◽  
Vol 280 (2) ◽  
pp. H634-H641 ◽  
Author(s):  
S. Bradley Forlow ◽  
Klaus Ley
Keyword(s):  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Striking Similarity ◽  
Leukocyte Rolling ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Recruitment ◽  
Adhesion Efficiency

To study selectin-independent leukocyte recruitment and the role of intercellular adhesion molecule-1 (ICAM-1), we generated mice lacking all three selectins and ICAM-1 (E/P/L/I−/−) by bone marrow transplantation. These mice were viable and appeared healthy under vivarium conditions, although they showed a 97% reduction in leukocyte rolling, a 63% reduction in leukocyte firm adhesion, and a 99% reduction of neutrophil recruitment in a thioglycollate-induced model of peritonitis at 4 and 24 h. Mononuclear cell recruitment was almost unaffected. All residual leukocyte rolling and most leukocyte adhesion in these mice depended on α4-integrins, but a small number of leukocytes (6% of wild-type control) still became adherent in the absence of all known rolling mechanisms (E-, P-, L-selectin and α4-integrins). A striking similarity of leukocyte adhesion efficiency in E/P/L−/− and E/P/I−/− mice suggests a pathway in which leukocyte rolling through L-selectin requires ICAM-1 for adhesion and recruitment. Comparison of our data with mice lacking individual or other combinations of adhesion molecules reveal that elimination of more adhesion molecules further reduces leukocyte recruitment but the effect is less than additive.

Role of ICAM-1 in chronic hepatic allograft rejection in the rat

2002 ◽  
Vol 283 (1) ◽  
pp. G196-G203 ◽  
Author(s):  
John Wong ◽  
Paul Kubes ◽  
Yikun Zhang ◽  
Yang Li ◽  
Stefan J. Urbanski ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Brown Norway ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Recruitment ◽  
Hepatic Allograft

The pathogenesis of hepatic allograft rejection remains unclear. We aimed to clarify the early role of intercellular adhesion molecule-1 (ICAM-1)-mediated cell recruitment in chronic hepatic rejection. Liver transplantation was performed from Lewis to Lewis rats (isograft controls) and from Lewis to Brown Norway rats (allograft rejection group). The allografted rats were treated with either ICAM-1 antisense oligonucleotides (10 mg · kg−1· day−1× 6 days ip) or a control preparation (either ICAM-1 missense oligonucleotide or normal saline). Hepatic leukocyte recruitment in vivo was studied on day 6 by using intravital microscopy. Liver histology, biochemistry, and survival rates were also examined. Leukocyte adhesion in terminal hepatic venules was significantly increased in the rejection group compared with isograft controls. Antisense ICAM-1 in the allografted group effectively reduced leukocyte adhesion. Histology and liver chemistry were less deranged in the antisense-treated groups compared with control-treated allografted rats. In the allograft groups, survival was significantly prolonged in the antisense-treated rats (42.3 ± 1.2 days) compared with the controls (25.2 ± 2.7 days). These results showed that early leukocyte recruitment in the hepatic microvasculature of rejecting allografts is ICAM-1 dependent and suggest that impacting on early cell recruitment can significantly ameliorate chronic rejection.

Control of leukocyte rolling velocity in TNF-α–induced inflammation by LFA-1 and Mac-1

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 336-341 ◽  
Author(s):  
Jessica L. Dunne ◽  
Christie M. Ballantyne ◽  
Arthur L. Beaudet ◽  
Klaus Ley
Keyword(s):  
Leukocyte Adhesion ◽  
Leukocyte Rolling ◽  
Rolling Velocity ◽  
Slowing Down ◽  
Tnf Α ◽  
Adhesion Efficiency ◽  
Factor Α ◽  
Rolling Leukocytes ◽  
Necrosis Factor ◽  
Β2 Integrins

Previously it was shown that β2-integrins are necessary for slow leukocyte rolling in inflamed venules. In this study, mice that are deficient for either one of the β2-integrins, αLβ2 (LFA-1) or αMβ2 (Mac-1), were used to determine which of the β2-integrins are responsible for slowing rolling leukocytes. The cremaster muscles of these mice were treated with tumor necrosis factor-α and prepared for intravital microscopy. The average rolling velocities in venules were elevated in LFA-1−/−mice (11.0 ± 0.7 μm/s) and Mac-1−/− mice (10.1 ± 1.1 μm/s) compared to wild-type mice (4.8 ± 0.3 μm/s;P < .05), but were lower than in CD18−/−mice (28.5 ± 2.1 μm/s). When both LFA-1 and Mac-1 were absent or blocked, rolling velocity became dependent on shear rate and approached that of CD18−/− mice. In addition, leukocyte adhesion efficiency was decreased in LFA-1−/− mice to near CD18−/− levels, but decreased only slightly in Mac-1−/− mice. Thus, both LFA-1 and Mac-1 contribute to slowing down rolling leukocytes, although LFA-1 is more important than Mac-1 in efficiently inducing firm adhesion.

scholarly journals CXCL1-Triggered Interaction of LFA1 and ICAM1 Control Glucose-Induced Leukocyte Recruitment during InflammationIn Vivo

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Kirsten Buschmann ◽  
Lutz Koch ◽  
Natascha Braach ◽  
Hanna Mueller ◽  
David Frommhold ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Leukocyte Adhesion ◽  
Flow Chamber ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Dependent Manner ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Models ◽  
Trauma Model

It is well acknowledged that proinflammatory stimulation during acute hyperglycemia is able to aggravate inflammatory diseases. However, the mechanisms of proinflammatory effects of glucose are controversially discussed. We investigated leukocyte recruitment after intravenous injection of glucose in different inflammatory models using intravital microscopy. Flow chamber experiments, expression analysis, functional depletion, and knockout of key adhesion molecules gave mechanistic insight in involved pathways. We demonstrated that a single injection of glucose rapidly increased blood glucose levels in a dose-dependent manner. Notably, during tumor necrosis factor (TNF)α-induced inflammation leukocyte recruitment was not further enhanced by glucose administration, whereas glucose injection profoundly augmented leukocyte adhesion and transmigration into inflamed tissue in the trauma model, indicating that proinflammatory properties of glucose are stimulus dependent. Experiments with functional or genetic inhibition of the chemokine receptor CXCR2, intercellular adhesion molecule 1 (ICAM1), and lymphocyte function antigen 1 (LFA1) suggest that keratino-derived-chemokine CXCL1-triggered interactions of ICAM1 and LFA1 are crucially involved in the trauma model of inflammation. The lacking effect of glucose onβ2integrin expression and on leukocyte adhesion in dynamic flow chamber experiments argues against leukocyte-driven underlying mechanisms and favours an endothelial pathway since endothelial ICAM1 expression was significantly upregulated in response to glucose.

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