Modulation of the adhesive responses of monocytic cells may reflect their motility at sites of diseased tissues (inflammation, tumors). Integrins α5β1 mediate fibronectin (Fn)-dependent adhesion of human monocytes and their precursors. The effect of type I IFNs (α, β) and type II IFN (γ) was assessed on the adhesive capacities of promonocytic U937 cells and monocytes. IFN-β and IFN-γ abrogated monocytic cell adhesion to Fn, but such impaired cell attachment was not due to altered levels of α5β1 integrins. In contrast, IFN-α did not affect cell adhesion to Fn. Participation of cytoskeleton assembly in IFN-mediated cell detachment was evaluated. Activation of RhoA activity with lysophosphatidic acid (LPA) increased 2-fold the adhesion of monocytic cells to Fn in a α5β1-mediated fashion, and IFN-γ treatment reversed the enhancing effect of LPA. Moreover, U937 cells and monocytes dominantly expressed the 44-46 kDa paxillin forms and IFN-β and IFN-γ led to the accumulation of 66-70 kDa paxillin forms. These results indicate that IFN-mediated loss of monocyte adhesion to Fn is associated with changes in the cytoskeleton associated proteins paxillin and Rho.

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