Evidence of CXC, CC and C chemokine production by lymphatic endothelial cells

Abstract

SUMMARYAlthough production of chemokines by vascular endothelial cells has been documented, there is only limited information regarding the expression of chemokines by the lymphatic endothelium. Here we used lymphatic endothelial cells (LEC) derived from experimentally induced murine lymphangiomas to investigate the pattern of chemokine expression by these cells. Histological analysis of the lymphatic hyperplasia revealed the presence of leucocytes in the tissues surrounding the lesions, suggesting the presence of chemoattractant activity. A functional chemotactic assay on human polymorphonuclear cells and on puri®ed subpopulations of murine leucocytes using culture supernatants from LEC primary cultures con®rmed the presence of chemoattractant activity. The identity of different cytokines of the CXC, CC and C subfamilies was investigated by reverse trancriptase±polymerase chain reaction on total endothelial cell RNA. Ampli®ed fragments corresponding to KC, IP10, Mig-1, BCL, MIP-2, SLC, RANTES, MCP-1, C10, and Lptn were obtained, and con®rmed by Southern blot and sequencing. In contrast, MIP-1a, MIP-1b, and MIP1g were not detected. Higher levels of expression were revealed by Northern blot analysis for Mig-1, MCP-1 and C10. The lymphatic endothelium-restricted production of these chemokines was also con®rmed by in situ hybridization. The presence of high C10 mRNA expression levels in LEC was particularly unexpected, because the production of this molecule has been previously identi®ed only in cells of the haematopoietic lineage. These observations represent the ®rst detailed analysis of chemokine production by lymphatic endothelial cells and may account, in part, for the mechanism of leucocyte recruitment into the lymphatics, and of lymphocyte recirculation within the lymphatic system.

Human Lymphatic Endothelial Cells Express Multiple Functional TLRs

“…Cells expressing receptors for these chemokines could be recruited into environments containing stimulated lymphatic vessels, and this may represent a pathway for the recirculation and clearance of immune effector cells during inflammation. Basal production of inflammatory chemokines by LECs has been reported (43) and our findings here demonstrate that PAMPs induce high levels of these inflammatory mediators. Such pathogen-driven inflammatory responses could contribute to dissemination of organisms, such as by CXCL8-mediated recruitment of neutrophils harboring live bacteria (44).…”

VEGF-C and VEGF-D Blockade Inhibits Inflammatory Skin Carcinogenesis

“…Macrophage inflammatory protein 1a (MIP-1a) and MCP-1 (CCL2), important macrophage chemoattractants, were among the several macrophage-associated cytokines found at lower levels in the transgenic skin and in transgenic papillomas. The DMBA-TPA-induced inflammatory response includes elevated expression of MIP-1a (31), whereas MCP-1 is expressed by lymphatic endothelial cells (32). Thus, the lack of lymphatic vessels likely contributed to the reduced MCP-1 levels and reduced macrophage numbers in transgenic skin.…”

Nonproteolytic Properties of Murine Alternatively Spliced Tissue Factor: Implications for Integrin-Mediated Signaling in Murine Models

“…Cxcl2 (a gene analogous to Il-8) encodes a major inflammatory chemokine involved in the recruitment of inflammatory cells (37,38), whereas Csf-1 production by stromal cells has been linked to the increased recruitment of tumor-associated macrophages and propagation of metastases (39). Genes encoding regulatory transcription factors were also upregulated in masTF-and hasTF-treated cells, for example, Cebpd and Cebpb.…”