Abundant expression of chemokines in malignant and infective human lymphadenopathies

Lymph nodes can be the primary target of infection or malignant transformat ion and may exhibit characteristic patterns of leukocyte infiltration analo gous to those seen in inflammation of other tissues. Leukocyte migration to lymph nodes in vivo is a highly regulated, multi-step process that depends upon adhesion molecules and as yet, uncharacterized chemotactic signals. C hemokines are a key part of the orchestrated code of signals that directs l eukocyte subsets to sites of inflammation or immune response. The potential role of these chemoattractants in selective trafficking of leukocyte subse ts into lymph nodes was assessed by determining the expression of chemokine s on a range of pathological and normal human lymph nodes and by evaluating the cellular composition of each lymph node. In situ hybridization using c hemokine riboprobes and immunohistochemistry using specific antibodies were performed in order to correlate the mRNA and protein expression of the che mokines, The cellular source(s) of each chemokine was assessed by immunohis tochemical staining of adjacent sections using antibodies directed against distinctive cellular markers, Substantial, but varied, expression of macrop hage inflammatory protein (MIP)-1 alpha, MIP-1 beta, RANTES, macrophage che motactic protein (MCP)-1, eotaxin, and interleukin 8 (IL-8) were detected i n the pathological lymph nodes by diverse cell types. Control lymph nodes s howed expression only of RANTES, mainly by high endothelial venules, In all lymph nodes, except the nodes infiltrated with breast cancer, chemokine mR NA expression was highly concordant with the corresponding protein. In cont rast with in vitro studies that have suggested discrete target cell specifi city of chemokines, this study showed that with the possible exception of t he neutrophil chemoattractant, IL-8, no chemokine appeared to be uniquely a ssociated with the accumulation of a specific leukocyte subset. These data implicate chemokines in the recruitment of leukocytes to lymph nodes affect ed by diverse disease states. (C) 1999 Academic Press.