Annexin II mediates plasminogen-dependent matrix invasion by human monocytes: enhanced expression by macrophages.
Monocytes and macrophages participate in a wide variety of host defense mechanisms. Annexin II, a fibrinolytic receptor, binds plasminogen and tissue plasminogen activator (t-PA) independently at the cell surface, thereby enhancing the catalytic efficiency of plasmin production. We demonstrated previously that annexin II on the surface of both cultured monocytoid cells and monocyte-derived macrophages promotes their ability to remodel extracellular matrix. Here, we demonstrate that human peripheral blood monocytes represent the major circulating annexin II-expressing cell. Annexin II supported t-PA-dependent generation of cell surface plasmin and the matrix-penetrating activity of human monocytes. Compared to polymorphonuclear leukocytes, monocytes supported a 12.9-fold greater rate of plasmin generation in the presence of exogenous t-PA, and this activity was largely attributable to annexin II. Likewise, anti-annexin II IgG directed against the t-PA-binding tail domain inhibited plasminogen-dependent, cytokine-directed monocyte migration through extracellular matrix. On differentiation of monocytes to macrophages, there was a 2.4-fold increase in annexin II-specific mRNA, and a 7.9-fold increase in surface annexin II. Thioglycolate-elicited peritoneal macrophages, furthermore, displayed an additional 3.8-fold increase in annexin II surface expression compared with resident cells. Thus, annexin II-mediated assembly of plasminogen and t-PA on monocyte/macrophages contributes to plasmin generation, matrix remodeling, and directed migration.
D017306:Annexin A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D010958:Plasminogen / Q000502:physiology*; D013864:Thioglycolates / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000502:physiology
D017306:Annexin A2; D007074:Immunoglobulin G; D013864:Thioglycolates; D010958:Plasminogen; D010959:Tissue Plasminogen Activator