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C-C Chan, D Shen, JJ Hackett, RR Buggage, N Tuaillon; Expression of Chemokine Receptors CXCR4 and CXCR5 and Chemokine BLC In Primary Intraocular Lymphoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2579.
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© ARVO (1962-2015); The Authors (2016-present)
. Purpose: Chemokines are a family of 8-10 kDa proteins with a range of biological activities including the regulation of leukocyte trafficking, modulation of hematopoietic cell proliferation and adhesion to extracellular matrix molecules. Specifically, BLC (B-lymphocyte chemoattractant) is chemotactic for human B cells, and CXCR4 and CXCR5 (ligand of BLC) are differentially expressed in B cells including malignant B cells. We investigated expression of BLC chemokine/chemokine receptors in eyes with primary intraocular lymphoma (PIOL). Methods: Three freshly enucleated eyes with PIOL of diffuse large B-cell phenotype were studied. Frozen sections were cut through the tumor. The slides were evaluated using immunohistochemistry (avidin-biotin-complex immunoperoxidase technique) for CXCR4, CXCR5, and BLC to detect the chemokine expression and location. RT-PCR was used to detect chemokine transcripts in PIOL and RPE cells following microdissection [either laser capture (Arcturus) or manual dissection] from frozen section slides. The chemokine primers were: CXCR4, 5'-CCT TCA TCA GTC TGG ACC GC-3' (sense) and 5'-CCT TGG CCT CTG ACT GTT GG-3' (antisense); CXCR5, 5'-ATA AGA CAG TGA CCA GTC TG-3' (sense) and 5'-TGG ACA ATG GCC AGG TAG CG-3' (antisense); and BLC, 5'-TCA TAG TCT GGA AGA AGA ACA AGT CAA-3' (sense) and 5'-TCA GCA TCA GGG AAT CTT TCT CT-3' (antisense). Results: The three eyes showed similar pathology with typical large B lymphoma cells at the RPE level and retina. The eyes also demonstrated similar chemokine profile. High expression levels of CXCR4 and CXCR5 were found and limited to the lymphoma cells. In contrast, BLC was weakly expressed in the RPE but not in other ocular resident cells. Expression of CXCR4 and CXCR5 transcripts was also detected abundantly in lymphoma cells. Interestingly, BLC transcripts were detected only in RPE cells surrounding the region infiltrated by PIOL cells. Conclusion: Chemokines and chemokine receptors selective for B cells were identified in RPE and malignant B-cells of these three cases of PIOL. BLC strongly attracts B-cells, while promoting migration of only small numbers of T cells and macrophages. We propose that BLC may be involved in PIOL by selectively attracting lymphoma cells between the RPE and Bruch's membrane. Inhibition of B-cell chemoattractants may be useful for the prevention and treatment of PIOL.
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