Role of the Renin-Angiotensin System in Human Conjunctival Lymphoma

Abstract

Purpose: The renin-angiotensin system (RAS), a known important controller of systemic blood pressure (circulatory RAS), plays distinct roles in inflammation and pathological vascular conditions in various organs including the eye (tissue RAS). Conjunctival lymphoma is one of the common malignancies found in the ocular adnexa. In this study, we investigated the role of RAS in extranodal marginal zone B-cell lymphoma (EMZL) of the conjunctiva.

Methods: Gene expressions of RAS components [prorenin, (pro)renin receptor ((P)RR), angiotensinogen, angiotensin converting enzyme, angiotensin II type 1 receptor (AT1R) and AT2R] in EMZL tissues surgically excised from patients were analyzed using reverse transcription PCR. Localization of AT1R and (P)RR in the EMZL tissues were studied by immunofluorescent analyses. Expression levels of pro-angiogenic and inflammatory genes in human B-lymphocyte cell lines treated with angiotensin II (Ang II) were analyzed by real-time PCR.

Results: Gene expressions of RAS components were detected in EMZL and several human B-lymphocyte cell lines. (P)RR and AT1R were detected in both vascular endothelial cells and the cytoplasm of atypical lymphoid cells, co-localized with CD31 (endothelial tissue marker) and CD20 (B lymphocyte marker), respectively. Immunofluorescent analyses showed co-localization of prorenin and angiotensinogen in (P)RR-positive and AT1R-positive cells, respectively. Real time-PCR analysis revealed that Ang II significantly upregulated several mRNA expression levels [e.g. basigin and vascular endothelial growth factor A], which were suppressed by pre-treatment of valsartan (AT1R blocker), in human B lymphocyte cell line.

Conclusions: Our data using clinical samples together with in vitro results provide evidence that tissue RAS is associated with pathological events in human conjunctival lymphoma.

Keywords: 744 tumors • 474 conjunctiva