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Human Serum-Induced Expression of E-selectin on Porcine Aortic Endothelial Cells in Vitro Is Totally Complement Mediated

Human Serum-Induced Expression of E-selectin on Porcine Aortic Endothelial Cells in Vitro Is Totally Complement Mediated

U Ø Sølvik, G Haraldsen, A E Fiane, E Boretti, J D Lambris, M Fung, E Thorsby, T E Mollnes

Transplantation. 2001 Dec 27;72(12):1967-73.

PMID: 11773897

Abstract:

Background:
Whereas complement is a key mediator of hyperacute xenograft rejection, its role in acute vascular rejection (AVR) is a matter of controversy. AVR is associated with de novo synthesis of endothelial cell-derived inflammatory mediators, including the leukocyte-recruiting adhesion molecule E-selectin. Here we investigate the role and mechanism of complement in human serum-induced porcine endothelial cell activation.
Methods:
An in vitro xenotransplantation method was designed using porcine aortic endothelial cells stimulated with human serum in microculture wells. E-selectin expression was measured by cell-enzyme immunoassay. Complement inhibitors acting at different levels in the cascade were investigated for their effect on E-selectin expression.
Results:
E-selectin was strongly induced by normal human serum but not by heat-inactivated serum. Compstatin, a synthetic C3 inhibitor, markedly reduced human serum-induced E-selectin expression. Purified C1-inhibitor suppressed E-selectin induction completely, indicating activation through the classical or lectin pathway. Furthermore, a monoclonal antibody (mAb) that inhibits cleavage of C5 or another mAb that blocks the function of C7, completely inhibited the expression of serum-induced E-selectin, consistent with the terminal C5b-9 complement complex being the mediator of the endothelial cell activation. Inhibition of the alternative pathway using a novel antifactor D mAb did not reduce E-selectin expression.
Conclusion:
Human serum-induced expression of porcine E-selectin is totally complement dependent, induced by a C1-inhibitor regulated pathway and mediated through the terminal complement complex. The data may have implications for therapeutic strategies, particularly of C1-inhibitor and anti-C5 mAb, to protect against endothelial cell activation and subsequent AVR of porcine xenografts.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP80295574	Complement C7 from human serum		80295-57-4	Price

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