The　acute　phase　reactant　C-reactive　protein　(CRP)　binds　with　high　affinity　to　fibronectin　(FN),　but　this　binding　occurs　only　at　pH　6.5　or　lower,　and　the　binding　is　inhibited　by　calcium　ions　at　physiological　pH.　Since　CRP　in　the　circulating　blood　exists　in　a　calcium-binding　form,　the　interaction　between　CRP　and　FN　in　vivo　has　been　uncertain.　CRP　can　undergo　a　conformational　rearrangement　in　the　absence　of　calcium　or　in　the　local　microenvironment　(e.g.,　acidic　pH)　of　inflamed　tissue　to　dissociate　into　monomeric　CRP　(mCRP).　Therefore,　we　tested　whether　these　discrepancies　can　be　explained　by　the　different　isoforms　and　locations　of　CRP.　Surface　plasmon　resonance　and　ELISA　assays　showed　that　mCRP　binds　with　high　affinity　to　FN,　and　the　binding　of　mCRP　to　FN　was　unaffected　by　calcium　or　pH.　Peptide　competition　assay,　deletion　mutant　binding　assay　and　protein　docking　analyse　verified　that　the　binding　site　of　mCRP　to　FN　is　residues　a.a.35-47.　Furthermore,　mCRP　can　significantly　enhance　the　adhesion　of　monocytes　to　FN　as　well　as　upregulate　the　adhesion　molecules　expression　on　endothelial　cell.　Colocalization　of　mCRP　with　FN　was　observed　in　mice　with　DSS-induced　colitis,　whereas　there　was　very　little　signal　orcolocalization　of　CRP.　These　results　provide　in　vitro　and　in　vivo　evidence　that　mCRP　formed　by　local　dissociation　from　circulating　CRP　is　the　major　isoform　that　interacts　with　FN　and　regulates　FN-mediated　monocyte　adhesion,　which　is　involved　in　the　pro-inflammatory　process.