Annexin II mediates plasminogen-dependent matrix invasion by human monocytes: enhanced expression by macrophages

Autor: Domenick J. Falcone, K.M. Faisal Khan, Arunkumar B. Deora, Andrew T. Jacovina, Menard M. Gertler, Rebecca Weintraub, Katherine A. Hajjar, Carrie Brownstein
Rok vydání: 2004
Předmět:
Zdroj: Blood. 103:317-324
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood-2003-04-1304
Popis: 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.
Databáze: OpenAIRE