In vivo validation of signaling pathways regulating human monocyte chemotaxis

Journal of Immunological Methods
Ashish BhattacharjeeMartha K Cathcart

Abstract

Identification of novel signal transduction pathways regulating monocyte chemotaxis can indicate unique targets for preventive therapies for treatment of chronic inflammatory diseases. To aid in this endeavor we report conditions for optimal transfection of primary human monocytes coupled with a new model system for assessing their chemotactic activity in vivo. This method can be used as a tool to identify the relevant signal transduction pathways regulating human monocyte chemotaxis to MCP-1 in the complex in vivo environment that were previously identified to regulate chemotaxis in vitro. MCP-1-dependent chemotaxis of monocytes is studied in an adoptive transfer model where human monocytes transfected with mutant cDNAs are transferred to mice followed by initiation of peritonitis. Harvesting peritoneal cells at 24 h diminishes the contribution of immunologic responses to the cross-species transfer. Validation of relevant regulatory molecules in vivo is critical for understanding the most relevant therapeutic targets for drug development.

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Citations

Jan 23, 2008·The Journal of Experimental Medicine·Ravi S MishraMartha K Cathcart
Dec 26, 2008·Journal of Lipid Research·Martha K Cathcart
Mar 12, 2013·Journal of Immunological Methods·Lindsay A HohsfieldChristian Humpel
Dec 6, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pradip DasAshish Bhattacharjee

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