Abstract
Monocyte chemoattractant protein-1 (MCP-1)/CCL2 is a chemokine regulating the recruitment of monocytes into sites of inflammation and cancer. MCP-1 can be produced by a variety of cell types, such as macrophages, neutrophils, fibroblasts, endothelial cells, and epithelial cells. Notably, macrophages produce high levels of MCP-1 in response to proinflammatory stimuli in vitro, leading to the hypothesis that macrophages are the major source of MCP-1 during inflammatory responses in vivo. In stark contrast to the hypothesis, however, there was no significant reduction in MCP-1 protein or the number of infiltrating macrophages in the peritoneal inflammatory exudates of myeloid cell-specific MCP-1-deficient mice in response to i.p injection of thioglycollate or zymosan A. Furthermore, injection of LPS into skin air pouch also had no effect on local MCP-1 production in myeloid-specific MCP-1-deficient mice. Finally, myeloid-specific MCP-1-deficiency did not reduce MCP-1 mRNA expression or macrophage infiltration in LPS-induced lung injury. These results indicate that non-myeloid cells, in response to a variety of stimulants, play a previously unappreciated role in innate immune responses as the primary source of MCP-1.
Highlights
Chemokines play a pivotal role in guiding leukocyte trafficking during inflammatory responses [1]
Especially macrophages, were enriched by incubating peritoneal exudates cells (PEC) in a tissue culture plate at 37°C for 3 h and removing non-adherent cells, almost 100% of the Monocyte chemoattractant protein-1 (MCP-1) allele was the mutated allele (Figure 1C). These results indicate that the MCP1 gene was effectively deleted in the myeloid cells of LysMCre+, MCP-1flox/flox mice
We previously demonstrated that i.p. injection of TG or zymosan A into normal mice induced the production of MCP-1 which peaked at 4 h and systemic MCP-1 deficiency significantly reduced the accumulation of macrophages into the peritoneal cavity [14]
Summary
Chemokines play a pivotal role in guiding leukocyte trafficking during inflammatory responses [1] This is considered their primary function, chemokines control the organization of the entire hematopoietic/lymphopoietic system, including the regulation of stem cell maturation, the formation of secondary lymphoid tissues, and angiogenesis [2,3,4,5]. Chemokines and their receptors are intimately involved in the orchestration of inflammatory responses, in the pathogenesis of acquired immunodeficiency syndrome [6] and the progression of cancer [7]. It remains unclear whether, in a complex environment of injured tissue, other cell types produce significant levels of MCP-1
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