Collagen phagocytosis by human extravillous trophoblast: Potential role introphoblastic invasion

OBJECTIVES: To study collagen phagocytosis by human extravillous trophoblas t. METHODS: First-trimester extravillous trophoblastic cell lines and primary trophoblast cell preparations were cultured in vitro with collage-coated fl uorescent latex beads and fluorescent-labeled collagen. Confocal microscopy was used to demonstrate internalization of collagen and beads. The effect of cytochalasin B, temperature, metabolic inhibitors, and cytokines was stu died by culturing trophoblast cells with tritiated collagen. Acridine orang e was used to stain for lysosomal compartments, and histochemical methods w ere used to demonstrate acid phosphatase in trophoblast cells. RESULTS: Both cell lines and primary culture cells internalize collagen and beads. Confocal microscopy unequivocally localized the phagocytosed materi al to the intracellular compartment. Inhibition by cytochalasin B and cultu re at 4C of uptake of [H-3] collagen suggested that the process was phagocy tosis. Cytokines and growth factors did not affect phagocytosis. Lysosomal compartments and acid phosphatase appear to colocalize. CONCLUSIONS: The continuous remodeling and turnover of collagen which occur in a wide variety of tissues under both physiologic and pathologic conditi ons ware thought to be mediated by two pathways: one external (involving re lease of proteolytic enzymes), and the other internal (involving phagocytos is). Similar remodeling events are likely to occur during trophoblast invas ion. Although current views emphasize the importance of the extracellular p athway, we postulate, on the basis of our findings, that both pathways are used, with the internal pathway probably being dominant. We hypothesize tha t the proteolytic enzymes (extracellular pathway) disrupt collagen matrices , thereby facilitating phagocytosis. It is teleologically sound to conceive of a dominant intracellular pathway, as it allows for more precise control of the process of invasion and is economical, as the products of collagen degradation can by used as energy sources or building blocks. Copyright (C) 1999 by the Society for Gynecologic Investigation.