IgA1 from HSP Patients Trigger Apoptosis and Inhibit Cytoskeletal Proteins in HUVEC

Liping Yuan, Wenjun Fei, Lin Wu, Ming Gui, Qin Zhang, Bo Hu

Department of Medical Technology, Anhui Medical College, Hefei, China.
Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, Hefei, China.

DOI: 10.4236/ojped.2014.41005                

Abstract

Background: Henoch-Schonlein purpura (HSP) is a kind of systemic small vessel vasculitis in children. Endothelium cells injury induced by IgA1 is considered important in the pathogenesis of HSP. Research found that the apoptosis of vein endothelial cells was related to the vasculitis in HSP patients. Purpose: To observe the effect of IgA1 from HSP patients on the apoptosis of HUVEC and firstly analyze the mechanism of the apoptosis of HUVEC induced by IgA1. Methods: HUVECs were cultured in 3 different conditional media with IgA1 from HSP patients, normal healthy children and simply medium (blank control). Serum IgA1 was purified by jacalin affinity chromatography. The rates of apoptosis in HUVEC incubated with IgA1 were determined by TUNEL method and flow cytometry, respectively. The expression of the cytoskeletal proteins, such as FAK, Vinculin and MLCK was detected with the methods of Real-time PCR and Westernblot, respectively. Results: The present study showed that the apoptosis rate of HUVEC by IgA1 isolated from HSP patients was higher than blank control (14.77% ± 2.23% vs 2.25% ± 0.77%) (P < 0.01) and the rate of HUVEC by IgA1 from normal healthy children was higher than blank control (9.97% ± 1.48% vs 2.25% ± 0.77%) (P < 0.01). The cytoskeletal proteins, such as FAK, Vinculin and MLCK expression were down-regulated in HUVEC co-cultured with IgA1 isolated from HSP patients for 24h. Conclusion: These findings firstly on IgA1 from HSP patients may induce apoptosis of vascular endothelial cells through inhibiting the cytoskeletal proteins expression. IgA1 may accelerate progression of HSP by inducing apoptosis of vascular endothelial cells.

Keywords

Henoch-Schönlein Purpura (HSP); Endothelial Cells; Immunoglobulin A; Apoptosis; Cytoskeletal Proteins

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Ballinger, S. (2003) Henoch-Schonlein Purpura. Current Opinion in Rheumatology, 15, 591-594. http://dx.doi.org/10.1097/00002281-200309000-00012
[2]	Le, X., Zeng, C.H., Bao, Z.X., He, Z.Q. and Li, X.D. (2005) Effect of Inflammatory Cytokines on the Vascular Endothelial Cells Injured of HSP Patients and Its Mechanism. Guang Dong Medicine, 26, 520-521. (In Chinese)
[3]	Yuan, L.P., Zhang, Q. and Lu, L. (2012) Apoptosis of Vascular Endothelial Cells from HSP Patients and Its Relation with Serum IgA. Chinese Journal of Immunology, 28, 81-83. (In Chinese)
[4]	Ozen, S., Ruperto, N., Dillon, M.J., Bagga, A., Barron, K., et al. (2006) EULAR/PReS Endorsed Consensus Criteria for the Classification of Childhood Vasculitides. Annals of the Rheumatic Diseases, 65, 936-941. http://dx.doi.org/10.1136/ard.2005.046300
[5]	Fukuda, R., et al., (2007) HIF-1 Regulates Cytochrome Oxidase Subunits to Optimize Efficiency of Respiration in Hypoxic Cells. Cell, 129, 111-122. http://dx.doi.org/10.1016/j.cell.2007.01.047
[6]	Yang, Y.H., Huang, Y.H., Lin, Y.L., Wang, L.C., Chuang, Y.H., et al. (2006) Circulating IgA from Acute Stage of Childhood Henoch-Schonlein Purpura Can Enhance Endothelial Interleukin (IL)-8 Production through MEK/ERK Signalling Pathway. Clinical & Experimental Immunology, 144, 247-253. http://dx.doi.org/10.1111/j.1365-2249.2006.03076.x
[7]	Zhang, Q., Lu, L. and Lin, D. (2008) Levels and Significance of IgA1 in Serum and Skin Lesions of Pediatric Patients with Anaphylactoid Purpura. Chinese Journal of Dermatology, 41, 55-56. (In Chinese)
[8]	Desouza, M., Gunning, P.W. and Stehn, J.R. (2012) The Actin Cytoskeleton as a Sensor and Mediator of Apoptosis. Bioarchitecture, 2, 75-87. http://dx.doi.org/10.4161/bioa.20975
[9]	Owen, K.A., Abshire, M.Y., Tilghman, R.W., Casanova, J.E. and Bouton, A.H. (2011) FAK Regulates Intestinal Epithelial Cell Survival and Proliferation during Mucosal Wound Healing. PLoS One, 6, e23123. http://dx.doi.org/10.1371/journal.pone.0023123
[10]	Peng, X., Nelson, E.S., Maiers, J.L. and DeMali, K.A. (2011) New Insights into Vinculin Function and Regulation. International Review of Cell and Molecular Biology, 287, 191-231. http://dx.doi.org/10.1016/B978-0-12-386043-9.00005-0
[11]	Wang, H.H., Nakamura, A., Yoshiyama, S., Ishikawa, R., Cai, N., Ye, L.H., Takano-Ohmuro, H. and Kohama, K. (2012) Down-Regulation of Myosin Light Chain Kinase Expression in Vascular Smooth Muscle Cells Accelerates Cell Proliferation: Requirement of Its Actin-Binding Domain for Reversion to Normal Rates. Journal of Pharmacological Sciences, 119, 91-96. http://dx.doi.org/10.1254/jphs. 11213SC
[12]	Woodfin, A., Voisin, M.B., Beyrau, M., Colom, B., Caille, D., Diapouli, F.M., Nash, G.B., Chavakis, T., Albelda, S.M., Rainger, G.E., Meda, P., Imhof, B.A. and Nourshargh S. (2011) The Junctional Adhesion Molecule JAM-C Regulates Polarized Transendothelial Migration of Neutrophils in Vivo. Nature Immunology, 12, 761-769. http://dx.doi.org/10.1038/ni.2062