Monocyte aggregation around agarose beads in collagen gels: a 3-dimensional model of early granuloma formation?

ABSTRACT

Granulomas consist of organised collections of macrophages showing evidence of activation in response to an agent localised within a tissue. To date, in vitro models of granuloma formation have failed to reproduce the histological appearance of a granuloma, which forms a characteristic three-dimensional structure. The use of 3-D collagen gels allows agarose beads and human mononuclear cells to be suspended together in a milieu which permit the two to interact. The interaction between agarose beads and mononuclear cells produces monocyte-macrophage aggregates within 24 h which resemble an early granuloma. The monocytes show evidence of activation by direct microscopy, electron microscopy and immunohistochemistry. This model should permit the laboratory testing of hypotheses describing granuloma formation.