Dj. Falcone et al., Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II, BLOOD, 97(3), 2001, pp. 777-784
Genetic evidence demonstrates the importance of plasminogen activation in t
he migration of macrophages to sites of injury and inflammation, their remo
val of necrotic debris, and their clearance of fibrin, These studies identi
fied the plasminogen binding protein annexin II on the surface of macrophag
es 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 EG
TA eluates, Ligand blots demonstrated that annexin II comigrates with one o
f several proteins in lysates and membranes derived from RAW264.7 macrophag
es that bind plasminogen. Preincubation of RAW264.7 macrophages with monocl
onal anti-annexin II IgG inhibited (35%) their binding of I-125-Lys-plasmin
ogen, Likewise, plasmin binding to human monocyte-derived macrophages and T
HP-I monocytes was inhibited (50% and 35%, respectively) when cells were pr
eincubated with anti-annexin II IgG. Inhibition of plasminogen binding to a
nnexin II on RAW264.7 macrophages significantly impaired their ability to a
ctivate plasminogen and degrade [H-3]. glucosamine-labeled extracellular ma
trices, The migration of THP-1 monocytes through a porous membrane, in resp
onse to monocyte chemotactic protein-1, was blocked when the membranes were
coated with extracellular matrix. The addition of plasminogen to the monoc
ytes restored their ability to migrate through the matrix-coated membrane,
Preincubation of THP-1 monocytes with anti-annexin II IgG inhibited (60%) t
heir plasminogen-dependent chemotaxis through the extracellular matrix, The
se studies identify annexin II as a plasminogen binding site on macrophages
and indicate an important role for annexin II in their invasive and degrad
ative phenotype. (C) 2001 by The American Society of Hematology.