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The Interaction between Circulating Complement Proteins and Cutaneous Microvascular Endothelial Cells in the Development of Childhood Henoch-Schönlein Purpura
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The Interaction between Circulating Complement Proteins and Cutaneous Microvascular Endothelial Cells in the Development of Childhood Henoch-Schönlein Purpura
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Journal Article
The Interaction between Circulating Complement Proteins and Cutaneous Microvascular Endothelial Cells in the Development of Childhood Henoch-Schönlein Purpura
2015
Overview
In addition to IgA, the deposition of complement (C)3 in dermal vessels is commonly found in Henoch-Schönlein purpura (HSP). The aim of this study is to elucidate the role of circulating complement proteins in the pathogenesis of childhood HSP.
Plasma levels of C3a, C4a, C5a, and Bb in 30 HSP patients and 30 healthy controls were detected by enzyme-linked immunosorbent assay (ELISA). The expression of C3a receptor (C3aR), C5a receptor (CD88), E-selectin, intercellular adhesion molecule 1 (ICAM-1), C3, C5, interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, and RANTES by human dermal microvascular endothelial cells (HMVEC-d) was evaluated either by flow cytometry or by ELISA.
At the acute stage, HSP patients had higher plasma levels of C3a (359.5 ± 115.3 vs. 183.3 ± 94.1 ng/ml, p < 0.0001), C5a (181.4 ± 86.1 vs. 33.7 ± 26.3 ng/ml, p < 0.0001), and Bb (3.7 ± 2.6 vs. 1.0 ± 0.6 μg/ml, p < 0.0001), but not C4a than healthy controls. Although HSP patient-derived acute phase plasma did not alter the presentation of C3aR and CD88 on HMVEC-d, it enhanced the production of endothelial C3 and C5. Moreover, C5a was shown in vitro to up-regulate the expression of IL-8, MCP-1, E-selectin, and ICAM-1 by HMVEC-d with a dose-dependent manner.
In HSP, the activation of the complement system in part through the alternative pathway may have resulted in increased plasma levels of C3a and C5a, which, especially C5a, may play a role in the disease pathogenesis by activating endothelium of cutaneous small vessels.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Child
/ Children
/ Complement System Proteins - metabolism
/ Endothelial Cells - cytology
/ Endothelial Cells - metabolism
/ Enzyme-linked immunosorbent assay
/ Female
/ Humans
/ Infant
/ Intercellular adhesion molecule 1
/ Lectins
/ Male
/ Medicine
/ Monocyte chemoattractant protein 1
/ Patients
/ Plasma
/ Proteins
/ Purpura, Schoenlein-Henoch - blood
/ Purpura, Schoenlein-Henoch - pathology
/ R&D
/ RANTES
/ Skin
