Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II.

TitlePlasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II.
Publication TypeJournal Article
Year of Publication2001
AuthorsFalcone DJ, Borth W, Khan KM, Hajjar KA
Date Published2001 Feb 01
KeywordsAnimals, Annexin A2, Cell Line, Chelating Agents, Chemotaxis, Egtazic Acid, Extracellular Matrix, Fibrinolysin, Humans, Immunoglobulin G, Lysine, Macrophages, Membrane Proteins, Mice, Monocytes, Plasminogen

Genetic evidence demonstrates the importance of plasminogen activation in the migration of macrophages to sites of injury and inflammation, their removal of necrotic debris, and their clearance of fibrin. These studies identified the plasminogen binding protein annexin II on the surface of macrophages and determined its role in their ability to degrade and migrate through extracellular matrices. Calcium-dependent binding of annexin II to RAW264.7 macrophages was shown using flow cytometry and Western blot analysis of EGTA eluates. Ligand blots demonstrated that annexin II comigrates with one of several proteins in lysates and membranes derived from RAW264.7 macrophages that bind plasminogen. Preincubation of RAW264.7 macrophages with monoclonal anti-annexin II IgG inhibited (35%) their binding of 125I-Lys-plasminogen. Likewise, plasmin binding to human monocyte-derived macrophages and THP-1 monocytes was inhibited (50% and 35%, respectively) when cells were preincubated with anti-annexin II IgG. Inhibition of plasminogen binding to annexin II on RAW264.7 macrophages significantly impaired their ability to activate plasminogen and degrade [3H]-glucosamine-labeled extracellular matrices. The migration of THP-1 monocytes through a porous membrane, in response to monocyte chemotactic protein-1, was blocked when the membranes were coated with extracellular matrix. The addition of plasminogen to the monocytes restored their ability to migrate through the matrix-coated membrane. Preincubation of THP-1 monocytes with anti-annexin II IgG inhibited (60%) their plasminogen-dependent chemotaxis through the extracellular matrix. These studies identify annexin II as a plasminogen binding site on macrophages and indicate an important role for annexin II in their invasive and degradative phenotype.

Alternate JournalBlood
PubMed ID11157497
Grant ListP01-HL46403 / HL / NHLBI NIH HHS / United States
R01-HL40819 / HL / NHLBI NIH HHS / United States
R01-HL42493 / HL / NHLBI NIH HHS / United States
Related Faculty: 
Domenick J. Falcone, Ph.D.

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