Abstract
Chemotactic factors locally secreted from tissues regulate leukocyte migration via cell membrane receptors that induce intracellular signals. It has been suggested that neutrophils stimulated by bacterial peptides secrete a secondary stimulant that enhances the chemotactic cell migration of the surrounding cells. This paracrine mechanism contributes to chemokine-dependent neutrophil migration, however, it has not yet been extensively studied in lymphocytes. In this study, we provide evidence that lymphocytes stimulated by the chemokine, CXCL12, affect the CXCR4-independent chemotactic response of the surrounding cells. We found that CXCR4-expressing lymphocytes or the conditioned medium from CXCL12-stimulated cells promoted CXCR4-deficient cell chemotaxis. In contrast, the conditioned medium from CXCL12-stimulated cells suppressed CCR7 ligand-dependent directionality and the cell migration speed of CXCR4-deficient cells. These results suggest that paracrine factors from CXCL12-stimulated cells navigate surrounding cells to CXCL12 by controlling the responsiveness to CCR7 ligand chemokines and CXCL12.
Highlights
The directed recruitment of cells by chemotactic factors is an important aspect of various biological processes, including wound healing, angiogenesis, the immune response, and cancer metastasis [1]
To assess the possibility that CXCL12-stimulated cells produce sec ondary chemoattractants that affect surrounding cell migration, we examined the effect of CXCL12-stimulated parental H9 cells (WT) on the surrounding CXCR4-KO cells
We found that CXCL12-Fc binding was significantly reduced in CXCR4-KO cells compared to WT
Summary
The directed recruitment of cells by chemotactic factors is an important aspect of various biological processes, including wound healing, angiogenesis, the immune response, and cancer metastasis [1]. Multiple chemokines, including CCL21/SLC, CCL19/ELC, CXCL12/stromal cell-derived factor 1 alpha, CXCL10/IP-10, and CXCL13/BLC, mediate chemokine gradient-dependent cell migration and contribute to efficient lymphocyte migration from the blood to the lymph nodes and Payer’s patches [4]. Both CCL21 and CCL19 bind to a common receptor, CCR7, which is critical for T cell trafficking through high endothelial venules in the lymph nodes and Payer’s patches [5,6]. In contrast to CXCR4, CXCR7 only contributes to lymphocyte migration to a minor extent due to its low expression level on leukocyte cell surfaces under homeostatic conditions [12]
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