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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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The expression of E-selectin and ICAM-1 by HMVEC-d.HMVEC-d were stimulated by C3a, C5a of different concentrations (0, 50, 100, 200 ng/ml), or TNF-α (10 ng/ml). Six hr and 18 hr later, the cells were harvested and analyzed for the expression of E-selectin (A) and ICAM-1 (B) by flow cytometry. The expression levels were presented as mean fluorescence intensity (MFI). * denotes p < 0.05, compared with the value of nontreated.
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pone.0120411.g005: The expression of E-selectin and ICAM-1 by HMVEC-d.HMVEC-d were stimulated by C3a, C5a of different concentrations (0, 50, 100, 200 ng/ml), or TNF-α (10 ng/ml). Six hr and 18 hr later, the cells were harvested and analyzed for the expression of E-selectin (A) and ICAM-1 (B) by flow cytometry. The expression levels were presented as mean fluorescence intensity (MFI). * denotes p < 0.05, compared with the value of nontreated.

Mentions: In addition to the effects on endothelial chemokines enhancement, we further evaluated the abilities of C3a and C5a to regulate the expression of adhesion molecules including E-selectin and ICAM-1 on HMVEC-d, that are critical molecules involving the PMN recruitment. As can be seen in Fig. 5, TNF-α which was used as a positive control had a powerful capacity to increase the expression of both E-selectin and ICAM-1 on HMVEC-d. C3a at different concentrations, however, did not alter the expression levels of E-selectin, whereas C5a could significantly enhance E-selectin expression on HMVEC-d with a dose-dependent relationship in this interaction (Fig. 5A). Similarly, there was a dose-dependent effect of C5a but not C3a on the enhancement of endothelial ICAM-1 expression (Fig. 5B). Of note, the original data were shown in Table 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 expression of E-selectin and ICAM-1 by HMVEC-d.HMVEC-d were stimulated by C3a, C5a of different concentrations (0, 50, 100, 200 ng/ml), or TNF-α (10 ng/ml). Six hr and 18 hr later, the cells were harvested and analyzed for the expression of E-selectin (A) and ICAM-1 (B) by flow cytometry. The expression levels were presented as mean fluorescence intensity (MFI). * denotes p < 0.05, compared with the value of nontreated.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0120411.g005: The expression of E-selectin and ICAM-1 by HMVEC-d.HMVEC-d were stimulated by C3a, C5a of different concentrations (0, 50, 100, 200 ng/ml), or TNF-α (10 ng/ml). Six hr and 18 hr later, the cells were harvested and analyzed for the expression of E-selectin (A) and ICAM-1 (B) by flow cytometry. The expression levels were presented as mean fluorescence intensity (MFI). * denotes p < 0.05, compared with the value of nontreated.
Mentions: In addition to the effects on endothelial chemokines enhancement, we further evaluated the abilities of C3a and C5a to regulate the expression of adhesion molecules including E-selectin and ICAM-1 on HMVEC-d, that are critical molecules involving the PMN recruitment. As can be seen in Fig. 5, TNF-α which was used as a positive control had a powerful capacity to increase the expression of both E-selectin and ICAM-1 on HMVEC-d. C3a at different concentrations, however, did not alter the expression levels of E-selectin, whereas C5a could significantly enhance E-selectin expression on HMVEC-d with a dose-dependent relationship in this interaction (Fig. 5A). Similarly, there was a dose-dependent effect of C5a but not C3a on the enhancement of endothelial ICAM-1 expression (Fig. 5B). Of note, the original data were shown in Table 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