Model of the antiadhesive effect of fibrinogen. A model of the proposed mechanism by which soluble fibrinogen inhibits leukocyte adhesion to the fibrin clot. (i) Plasma fibrinogen interacts with fibrin clot, forming a layer consisting of loosely bound molecules. This results in the formation of a “feeble” adhesive substrate. Under flow conditions, fibrinogen in the stream is in dynamic equilibrium with surface-bound fibrinogen. (ii) Flowing leukocytes can engage either the insoluble fibrin matrix (cell 1) or fibrinogen bound to the surface of the clot (cells 2 and 3). (iii) There are 2 main sequels for cells, depending on the substrate to which they adhere. Leukocytes that attach directly to the fibrin matrix remain adherent (cell 1), whereas cells that engage loosely bound molecules in the fibrinogen-fibrin layer (cells 2 and 3) slip off, not being able to hold the clot. (iv) The vacant binding sites on the fibrin clot are replenished with new fibrinogen molecules from an abundant pool of flowing fibrinogen which renew the antiadhesive layer, and new leukocytes approach the clot making either brief encounters or stable adhesions. Soluble fibrinogen is depicted as a 3-modular structure. Leukocytes are depicted as shaded balls with integrins shown as dark rectangles.