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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 C3a receptor (C3aR) and C5a receptor (CD88) by HMVEC-d.HMVEC-d were pre-incubated with plasma of patients (N = 30) with acute HSP, plasma of healthy controls (N = 30), or culture medium alone for 48 hr, and then the cells were harvested and analyzed for the expression of C3aR (A) and CD88 (B) by flow cytometry. The expression levels were presented as mean fluorescence intensity (MFI).
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pone.0120411.g003: The expression of C3a receptor (C3aR) and C5a receptor (CD88) by HMVEC-d.HMVEC-d were pre-incubated with plasma of patients (N = 30) with acute HSP, plasma of healthy controls (N = 30), or culture medium alone for 48 hr, and then the cells were harvested and analyzed for the expression of C3aR (A) and CD88 (B) by flow cytometry. The expression levels were presented as mean fluorescence intensity (MFI).

Mentions: The interaction between C3a/C5a and HMVEC-d was subsequently studied to explore the possible contribution of such bioactive complement proteins to HSP development. First, the expression of C3a and C5a receptors by HMVEC-d was analyzed. Fig. 3 showed that HMVEC-d constitutively expressed C3aR and CD88 (isotype control vs medium only). Moreover, the endothelial expression levels of both C3aR (Fig. 3A) and CD88 (Fig. 3B) were not significantly affected by the incubation with plasma of patients with acute HSP (HSP plasma vs control plasma, C3a: 11.9 ± 0.6 vs 13.2 ± 2.4, p = 0.56; C5a: 25.5 ± 4.1 vs 24.3 ± 0.3 ng/ml, p = 0.65).


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 C3a receptor (C3aR) and C5a receptor (CD88) by HMVEC-d.HMVEC-d were pre-incubated with plasma of patients (N = 30) with acute HSP, plasma of healthy controls (N = 30), or culture medium alone for 48 hr, and then the cells were harvested and analyzed for the expression of C3aR (A) and CD88 (B) by flow cytometry. The expression levels were presented as mean fluorescence intensity (MFI).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0120411.g003: The expression of C3a receptor (C3aR) and C5a receptor (CD88) by HMVEC-d.HMVEC-d were pre-incubated with plasma of patients (N = 30) with acute HSP, plasma of healthy controls (N = 30), or culture medium alone for 48 hr, and then the cells were harvested and analyzed for the expression of C3aR (A) and CD88 (B) by flow cytometry. The expression levels were presented as mean fluorescence intensity (MFI).
Mentions: The interaction between C3a/C5a and HMVEC-d was subsequently studied to explore the possible contribution of such bioactive complement proteins to HSP development. First, the expression of C3a and C5a receptors by HMVEC-d was analyzed. Fig. 3 showed that HMVEC-d constitutively expressed C3aR and CD88 (isotype control vs medium only). Moreover, the endothelial expression levels of both C3aR (Fig. 3A) and CD88 (Fig. 3B) were not significantly affected by the incubation with plasma of patients with acute HSP (HSP plasma vs control plasma, C3a: 11.9 ± 0.6 vs 13.2 ± 2.4, p = 0.56; C5a: 25.5 ± 4.1 vs 24.3 ± 0.3 ng/ml, p = 0.65).

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