Adhesion molecules as determinants of disease: From molecular biology to surgical research

Menger, Michael D.; Vollmar, Brigitte

doi:10.1002/bjs.1800830506

Cited by 109 publications

(58 citation statements)

References 186 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it is dramatically up-regulated after stimulation with cytokines (IL-1h, IFN-g, TNF-a) or endotoxin (LPS). The expression of ICAM-1 by vascular endothelium is a characteristic feature of inflammatory immune responses, mediating the process of leucocyteendothelial cell interaction by binding to integrins 16 . PECAM-1 is constitutively expressed on endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Endothelial cell expression of adhesion molecules is induced by fetal plasma from pregnancies with umbilical placental vascular disease

Wang¹

2002

BJOG: An International Journal of Obstetrics and Gynaecology

View full text Add to dashboard Cite

Objective To test the hypothesis that local production with spill into the fetal circulation of factor(s) injurious to endothelium is responsible for the vascular pathology present when the umbilical artery Doppler study is abnormal. Expression of adhesion molecules is a feature of endothelial cell activation. Design Case -control study.Setting University teaching hospital.Samples Fetal plasma was collected from 27 normal pregnancies, 39 pregnancies with umbilical placental vascular disease defined by abnormal umbilical artery Doppler and 11 pregnancies with pre-eclampsia and normal umbilical artery Doppler. Methods Isolated and cultured human umbilical vein endothelial cells from normal pregnancies were incubated with fetal plasma from three study groups. mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) were assessed by reverse transcription-polymerase chain reaction. To confirm the occurrence of this in vivo, we measured the levels of soluble fractions of sICAM-1, sVCAM-1 and sPECAM-1 in the fetal circulation in the fetal plasma used for endothelial cell incubation. Results The mRNA expression of ICAM-1 [median 1.1 (interquartile range 0.5-1.9) vs 0.7 (0.3 -1.2), P < 0.05] and PECAM-1 [2.1 (1.2 -3.0) vs 1.5 (0.7 -2.1), P < 0.05] was significantly higher following incubation with fetal plasma from umbilical placental vascular disease compared with the normal group. There was no difference in the expression of VCAM-1 [1.2 (0.9 -1.8) vs 1.1 (0.8 -1.6), ns]. The group with maternal preeclampsia and normal umbilical artery Doppler did not differ from the normal group. In the umbilical placental vascular disease group, the results were similar in the presence or absence of pre-eclampsia. For soluble fractions of the adhesion molecules released into the fetal circulation, we found the levels (ng/mL) of sICAM-1 [median 248.5 (interquartile range 197.3 -315.7) vs 174.2 (144.5 -212.9), P < 0.05] and sPECAM-1 [9.3 (6.2 -11

show abstract

Section: Discussionmentioning

confidence: 99%

Endothelial cell expression of adhesion molecules is induced by fetal plasma from pregnancies with umbilical placental vascular disease

Wang¹

2002

BJOG: An International Journal of Obstetrics and Gynaecology

View full text Add to dashboard Cite

show abstract

“…Novel strategies in the control of inflammation may involve systemic administration of antisense oligonucleotides or antibodies against adhesion molecules, or antioxidants (Haller et al, 1996;Menger and Vollmar, 1996). Targeted expression of the inflamed tissue remains, however, difficult.…”

Section: Some Considerations Concerning Modulation Of the Heme-hemmentioning

confidence: 99%

Different Faces of the Heme-Heme Oxygenase System in Inflammation

Wagener

Volk

Willis

et al. 2003

Pharmacological Reviews

494

410

View full text Add to dashboard Cite

“…Sustained or dysregulated integrin activation, resulting in abnormal neutrophil trafficking, as well as direct damage to the vasculature and the underlying tissue, is known to contribute to sepsis. [2][3][4] Recombinant human activated protein C (rhAPC), the only FDA-approved drug for treating severe sepsis, is a vitamin K-dependent serine protease that is derived from protein C (PC). Activated protein C (APC) is most well known for its anticoagulant functions.…”

Section: Introductionmentioning

confidence: 99%

Recombinant human activated protein C inhibits integrin-mediated neutrophil migration

Elphick

Sarangi

Hyun

et al. 2009

Blood

View full text Add to dashboard Cite

Integrin-mediated cell migration is central to many biologic and pathologic processes. During inflammation, tissue injury results from excessive infiltration and sequestration of activated leukocytes. Recombinant human activated protein C (rhAPC) has been shown to protect patients with severe sepsis, although the mechanism underlying this protective effect remains unclear. Here, we show that rhAPC directly binds to ␤ 1 and ␤ 3 integrins and inhibits neutrophil migration, both in vitro and in vivo. We found that human APC possesses an Arg-Gly-Asp (RGD) sequence, which is critical for the inhibition. Mutation of this sequence abolished both integrin binding and inhibition of neutrophil migration. In addition, treatment of septic mice with a RGD peptide recapitulated the beneficial effects of rhAPC on survival. Thus, we conclude that leukocyte integrins are novel cellular receptors for rhAPC and the interaction decreases neutrophil recruitment into tissues, providing a potential mechanism by which rhAPC may protect against sepsis. IntroductionMigration of leukocytes to infection sites is vital for pathogen clearance and, thus, host survival. 1 Interaction of cell surface integrins with their counterpart ligands, which are expressed on the endothelial surface, results in the localization and adherence of circulating neutrophils to endothelial cells. This is followed by neutrophil activation and directed migration to sites of infection through the extracellular matrix. An important function of integrins is to concentrate neutrophils at the infection site, ensuring that their immune products and activities remain at this site, while minimizing unnecessary injury to uninfected tissues. Sustained or dysregulated integrin activation, resulting in abnormal neutrophil trafficking, as well as direct damage to the vasculature and the underlying tissue, is known to contribute to sepsis. [2][3][4] Recombinant human activated protein C (rhAPC), the only FDA-approved drug for treating severe sepsis, is a vitamin K-dependent serine protease that is derived from protein C (PC). Activated protein C (APC) is most well known for its anticoagulant functions. Although initial hypotheses to explain its efficacy in preventing severe sepsis centered on the antithrombotic and profibrinolytic functions of rhAPC, 5-8 other agents including antithrombin III and tissue-factor pathway inhibitor, known to have potent effects on such pathways, did not demonstrate the same clinical efficacy in the treatment of severe sepsis as rhAPC, 9,10 suggesting the ability of APC to improve several immunerelated functions independent of its anticoagulant functions. Although regulation of leukocyte migration has been proposed to underlie the protective effects of APC against sepsis, 11-16 the molecular mechanisms of the inhibitory effects of APC have not been demonstrated. Methods ReagentsRecombinant human APC (rhAPC) was obtained from Eli Lilly (Indianapolis, IN). The protein C mutant containing Glu substitution in place of Asp-222 (D222E) was constructed by...

show abstract

Adhesion molecules as determinants of disease: From molecular biology to surgical research

Cited by 109 publications

References 186 publications

Endothelial cell expression of adhesion molecules is induced by fetal plasma from pregnancies with umbilical placental vascular disease

Endothelial cell expression of adhesion molecules is induced by fetal plasma from pregnancies with umbilical placental vascular disease

Different Faces of the Heme-Heme Oxygenase System in Inflammation

Recombinant human activated protein C inhibits integrin-mediated neutrophil migration

Contact Info

Product

Resources

About