Galectin-1 co-clusters CD43/CD45 on dendritic cells and induces cell activation and migration through syk and protein kinase C signaling

Jennifer A. Fulcher, Margaret H. Chang, Shuo Wang, Tim Almazan, Sara T. Hashimi, Anna U. Eriksson, Xiangshu Wen, Mabel Pang, Linda G. Baum, Ram Raj Singh, Benhur Lee

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Galectin-1 is a galactoside-binding lectin expressed in multiple tissues that has pleiotropic immunomodulatory functions. We previously showed that galectin-1 activates human monocyte-derived dendritic cells (MDDCs) and triggers a specific genetic program that up-regulates DC migration through the extracellular matrix, an integral property of mucosal DCs. Here, we identify the galectin-1 receptors on MDDCs and immediate downstream effectors of galectin-1-induced MDDC activation and migration. Galectin-1 binding to surface CD43 and CD45 on MDDCs induced an unusual unipolar co-clustering of these receptors and activates a dose-dependent calcium flux that is abrogated by lactose. Using a kinome screen and a systems biology approach, we identified Syk and protein kinase C tyrosine kinases as mediators of the DC activation effects of galectin-1. Galectin-1, but not lipopolysaccharide, stimulated Syk phosphorylation and recruitment of phosphorylated Syk to the CD43 and CD45 co-cluster on MDDCs. Inhibitors of Syk and protein kinase C signaling abrogated galectin-1-induced DC activation as monitored by interleukin-6 production; and MMP-1, -10, and -12 gene up-regulation; and enhanced migration through the extracellular matrix. The latter two are specific features of galectin-1-activated DCs. Interestingly, we also found that galectin-1 can prime DCs to respond more quickly to low dose lipopolysaccharide stimulation. Finally, we underscore the biological relevance of galectin-1-enhanced DC migration by showing that intradermal injection of galectin-1 in MRL-fas mice, which have a defect in skin DC emigration, increased the in vivo migration of dermal DCs to draining lymph nodes.

Original languageEnglish
Pages (from-to)26860-26870
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number39
DOIs
StatePublished - 25 Sep 2009
Externally publishedYes

Fingerprint

Dive into the research topics of 'Galectin-1 co-clusters CD43/CD45 on dendritic cells and induces cell activation and migration through syk and protein kinase C signaling'. Together they form a unique fingerprint.

Cite this