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Blood, 1 January 2004, Vol. 103, No. 1, pp. 317-324.
Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-04-1304.
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PHAGOCYTES
Annexin II mediates plasminogen-dependent matrix invasion by human monocytes: enhanced expression by macrophages
Carrie Brownstein,
Arunkumar B. Deora,
Andrew T. Jacovina,
Rebecca Weintraub,
Menard Gertler,
K. M. Faisal Khan,
Domenick J. Falcone, and
Katherine A. Hajjar
From the Departments of Cell and Developmental Biology, Pediatrics, Medicine, and Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY.
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.
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