Characterization of Th1- and Th2-associated chemokine receptor expression in spleens of patients with immune thrombocytopenia.

Abstract

PURPOSE:

In view of the numerous clinical observations and laboratory studies that suggest a critical role for the spleen in immune thrombocytopenia (ITP) pathophysiology, we aimed to characterize Th1-associated chemokine receptors CXCR3 and CCR5 and Th2-associated chemokine receptor CCR3 in spleens of ITP patients and assess the significance of their differential expression in the clinical setting.

METHODS:

The histopathology of spleens was observed using hematoxylin-eosin staining (HE), and the positive rate of CXCR3, CCR5 and CCR3 expression in spleens of 24 ITP patients and 12 patients with traumatic splenic rupture as normal controls was detected by immunohistochemistry using the SP method. CXCR3, CCR5 and CCR3 protein expression was analyzed by Western blot and mRNA levels were investigated by real-time polymerase chain reaction (RT-PCR).

RESULTS:

Reactive hyperplasia could be seen in follicles of the white pulp, the germinal central zone was enlarged and the marginal zone was thickened, the central arteries were thickened and fibrotic, and the density of the capillary vessel was increased in ITP patients. ITP group displayed a higher rate of expression of Th1-associated chemokine receptors CXCR3 and CCR5 (83.3% vs. 75%, 100% vs. 83.3%) but lower rate of expression of Th2-associated chemokine receptor CCR3 (50% vs. 66.7%) compared with the controls (P < 0.05, respectively). Western blot analysis revealed that CXCR3 and CCR5 protein expression was significantly increased in ITP patients while CCR3 was significantly reduced (P < 0.05, respectively). Meanwhile, ITP patients displayed increased mRNA levels of CXCR3 and CCR5 but decreased gene expression of CCR3 (P < 0.05, respectively).

CONCLUSION:

The data suggested that the abnormal expression of Th1/Th2 chemokine receptors may participate in splenic immune disorder in patients with ITP. Using corresponding inhibitors may inhibit Th1-dominant expression and mitigate the progress of the disease.

• Authors: Shu-Fen Zhou, Ji Ma, Hui-Ting Qu, Zong-Tang Liu, Wei-Dong He, Juan-Dong Wang, Ai-Xia Dou, Ni Zhang, Jun-Li Liu, Cheng-Shan Guo, Yan Shi, Ming Hou, Jun Peng
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 33 Issue 5 Pg. 938-46 (Jul 2013) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 23494742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCR3 protein, human
• CXCR3 protein, human
• RNA, Messenger
• Receptors, CCR3
• Receptors, CCR5
• Receptors, CXCR3
• Receptors, Chemokine

Topics

• Adolescent
• Adult
• Arteries (immunology, metabolism, pathology)
• Child
• Female
• Humans
• Hyperplasia (genetics, immunology, metabolism, pathology)
• Male
• Microvessels (immunology, metabolism, pathology)
• Middle Aged
• RNA, Messenger (genetics)
• Receptors, CCR3 (genetics, immunology, metabolism)
• Receptors, CCR5 (genetics, immunology, metabolism)
• Receptors, CXCR3 (genetics, immunology, metabolism)
• Receptors, Chemokine (biosynthesis, genetics, immunology)
• Spleen (immunology, metabolism, pathology)
• Th1 Cells (immunology, metabolism, pathology)
• Th2 Cells (immunology, metabolism, pathology)
• Thrombocytopenia (genetics, immunology, metabolism, pathology)
• Young Adult