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The interaction between circulating complement proteins and cutaneous microvascular endothelial cells in the development of childhood Henoch-Schönlein Purpura.

Yang YH, Tsai IJ, Chang CJ, Chuang YH, Hsu HY, Chiang BL - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.

ABSTRACT

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Related in: MedlinePlus

The serum levels of C3 and C4 in 30 HSP patients.Serum C3 (A) and C4 (B) levels were detected by nephelometry in HSP patients between acute and convalescent stages. * denotes p < 0.001.
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pone.0120411.g001: The serum levels of C3 and C4 in 30 HSP patients.Serum C3 (A) and C4 (B) levels were detected by nephelometry in HSP patients between acute and convalescent stages. * denotes p < 0.001.

Mentions: To clarify the activation of complement in HSP, we first evaluated the serum levels of C3 and C4 in patients at both acute and convalescent stages. The results showed that C3 and C4 serum levels in all patients, no matter at acute stage or at convalescent stage, were within normal ranges (reference values, C3: 90–180 mg/dl, C4: 10–40 mg/dl). However, C3 (Fig. 1A) but not C4 (Fig. 1B) serum levels were significantly decreased when the disease subsided (C3: 128.8 ± 14.3 vs 111.8 ± 17.0 mg/dl, p < 0.001; C4: 26.6 ± 8.3 vs 22.8 ± 10.1 mg/dl, p = 0.1).


The interaction between circulating complement proteins and cutaneous microvascular endothelial cells in the development of childhood Henoch-Schönlein Purpura.

Yang YH, Tsai IJ, Chang CJ, Chuang YH, Hsu HY, Chiang BL - PLoS ONE (2015)

The serum levels of C3 and C4 in 30 HSP patients.Serum C3 (A) and C4 (B) levels were detected by nephelometry in HSP patients between acute and convalescent stages. * denotes p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356510&req=5

pone.0120411.g001: The serum levels of C3 and C4 in 30 HSP patients.Serum C3 (A) and C4 (B) levels were detected by nephelometry in HSP patients between acute and convalescent stages. * denotes p < 0.001.
Mentions: To clarify the activation of complement in HSP, we first evaluated the serum levels of C3 and C4 in patients at both acute and convalescent stages. The results showed that C3 and C4 serum levels in all patients, no matter at acute stage or at convalescent stage, were within normal ranges (reference values, C3: 90–180 mg/dl, C4: 10–40 mg/dl). However, C3 (Fig. 1A) but not C4 (Fig. 1B) serum levels were significantly decreased when the disease subsided (C3: 128.8 ± 14.3 vs 111.8 ± 17.0 mg/dl, p < 0.001; C4: 26.6 ± 8.3 vs 22.8 ± 10.1 mg/dl, p = 0.1).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.

ABSTRACT

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus