Expression pattern and cellular sources of chemokines in primary central nervous system lymphoma
- 289 Downloads
The expression pattern of a subset of chemokines and their corresponding receptors was investigated in primary central nervous system lymphomas (PCNSL). The tumor cells consistently expressed CXCR4, CXCL12, CXCR5, and CXCL13, both at mRNA and protein levels. Cerebral endothelial cells were positive for CXCL12 and CXCL13, while reactive astrocytes and microglial cells expressed CXCL12, CCR5, and CCR6. Inflammatory T cells in PCNSL were characterized by CCR5 and CCR6 positivity. Taken together, our data indicate a cell type-specific repertoire of chemokine and chemokine receptor expression in PCNSL suggesting that chemokine-mediated interactions facilitate crossing of the blood-brain barrier as well as intracerebral dissemination of PCNSL cells. In addition, chemokines expressed by tumor cells may contribute to induction of reactive glial changes and influence the composition of inflammatory infiltrates in PCNSL. Therefore, cell type specific expression of distinct chemokine profiles likely plays a role in the pathogenesis of PCNSL and may contribute to their characteristic histological appearance.
KeywordsPCNSL Chemokines Astrocytes Microglia Cerebral endothelial cells
The expert technical assistance of Irmgard Henke and Elena Fischer is gratefully acknowledged. This study was supported by the Deutsche Krebshilfe/Dr. Mildred Scheel Stiftung für Krebsforschung (grant no: 10-2153-De1).
- 4.Chunsong H, Yuling H, Li W, Jie X, Gang Z, Qiuping Z, Qingping G, Kejian Z, Li Q, Chang AE, Youxin J, Jinquan T (2006) CXC chemokine ligand 13 and CC chemokine ligand 19 cooperatively render resistance to apoptosis in B cell lineage acute and chronic lymphocytic leukemia CD23 + CD5 + B cells. J Immunol 177:6713–6722PubMedGoogle Scholar
- 5.Cook DN, Prosser DM, Forster R, Zhang J, Kuklin NA, Abbondanzo SJ, Niu XD, Chen SC, Manfra DJ, Wiekowski MT, Sullivan LM, Smith SR, Greenberg HB, Narula SK, Lipp M, Lira SA (2000) CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity 12:495–503PubMedCrossRefGoogle Scholar
- 6.Courts C, Montesinos-Rongen M, Martin-Subero JI, Brunn A, Siemer D, Zuhlke-Jenisch R, Pels H, Jurgens A, Schlegel U, Schmidt-Wolf IG, Schaller C, Reifenberger G, Sabel M, Warnecke-Eberz U, Wiestler OD, Kuppers R, Siebert R, Deckert M (2007) Transcriptional profiling of the nuclear factor-kappaB pathway identifies a subgroup of primary lymphoma of the central nervous system with low BCL10 expression. J Neuropathol Exp Neurol 66:230–237PubMedCrossRefGoogle Scholar
- 10.Gatter K, Warnke R (2001) Diffuse large cell lymphomas. Lyon, France, pp 171–174Google Scholar
- 11.Greaves DR, Wang W, Dairaghi DJ, Dieu MC, Saint-Vis B, Franz-Bacon K, Rossi D, Caux C, McClanahan T, Gordon S, Zlotnik A, Schall TJ (1997) CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3alpha and is highly expressed in human dendritic cells. J Exp Med 186:837–844PubMedCrossRefGoogle Scholar
- 13.Hieshima K, Imai T, Opdenakker G, Van Damme J, Kusuda J, Tei H, Sakaki Y, Takatsuki K, Miura R, Yoshie O, Nomiyama H (1997) Molecular cloning of a novel human CC chemokine liver and activation-regulated chemokine (LARC) expressed in liver. Chemotactic activity for lymphocytes and gene localization on chromosome 2. J Biol Chem 272:5846–5853PubMedCrossRefGoogle Scholar
- 17.Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisakk P, Ransohoff RM, Hofbauer M, Farina C, Derfuss T, Hartle C, Newcombe J, Hohlfeld R, Meinl E (2006) Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 129:200–211PubMedCrossRefGoogle Scholar
- 21.Montesinos-Rongen M, Kuppers R, Schluter D, Spieker T, Van Roost D, Schaller C, Reifenberger G, Wiestler OD, Deckert-Schluter M (1999) Primary central nervous system lymphomas are derived from germinal-center B cells and show a preferential usage of the V4–34 gene segment. Am J Pathol 155:2077–2086PubMedGoogle Scholar
- 26.Paulus W, Jellinger K, Morgello S, Deckert-Schlüter M (2000) Malignant lymphomas. Lyon, France, pp 198–203Google Scholar
- 33.Stumm RK, Rummel J, Junker V, Culmsee C, Pfeiffer M, Krieglstein J, Hollt V, Schulz S (2002) A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia. J Neurosci 22:5865–5878PubMedGoogle Scholar