Loss of alpha5beta1-mediated adhesion of monocytic cells to fibronectin by interferons beta and gamma is associated with changes in actin and paxillin cytoskeleton.
BACKGROUND
Modulation of the adhesive responses of monocytic cells may reflect their motility within the bone marrow and at sites of inflammation. Monocyte alpha5beta1 integrins mediate fibronectin-dependent adhesion. We previously showed that type II IFN-gamma reduces adhesiveness to fibronectin (Fn) whereas TGF-beta1 enhances cell attachment. Here, we investigate the role of type I IFNs (alpha, beta) on the adhesive capacity of monocytic cells.


METHODS
The influence of IFNs on the human U937 cell line adhesion to fibronectin-coated surfaces was determined. The expression of integrins and cytoskeleton proteins was analyzed by FACS, Western blotting and/or fluorescence microscopy analyses.


RESULTS
IFN-alpha did not affect cell adhesion to fibronectin. In contrast, IFN-beta, like IFN-gamma, abrogated U937 adhesion to fibronectin and antagonized TGF-beta1-mediated cell attachment to Fn. The impaired binding of IFN-beta- and IFN-gamma-treated cells to fibronectin was not due to reduced levels of alpha5beta1 integrins. IFN-beta and IFN-gamma re-organized filamentous actin, and such rearrangement differed from that observed in TGF-beta1-adhesive cells. U937 cells dominantly expressed 44 to 46 kDa paxillin forms and treatment with IFNs enhanced the number of 66 to 70 kDa forms of paxillin.


CONCLUSIONS
Our data show that IFN-beta and IFN-gamma induced loss of monocytic adhesion to fibronectin associated with changes in actin and paxillin cytoskeleton, thereby pointing to a possible effect of these cytokines in monocyte trafficking.
Surin
B
B
Unité 365 INSERM, Institut Curie, 75231 Paris cedex 05, France.
Rouillard
D
D
Bauvois
B
B
D000199:Actins / Q000502:physiology; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D051419:Paxillin; D010750:Phosphoproteins / Q000502:physiology; D017469:Receptors, Fibronectin / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D020298:U937 Cells
D000199:Actins; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D017469:Receptors, Fibronectin; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016899:Interferon-beta; D007371:Interferon-gamma