Possible role for cellular FXIII in monocyte-derived dendritic cell motility.
The A subunit of plasma factor XIII (FXIII-A) is thought to function as an intracellular transglutaminase (TG) in the monocyte/macrophage lineage to regulate certain intracellular processes involving cytoskeleton remodeling, but its precise role and the functional consequences of its absence remain poorly understood. In the present study, we show that cellular FXIII (cFXIII) expression is largely upregulated during in vitro differentiation of monocytes into dendritic cells (DCs). Monodansyl-cadaverine, a competitive substrate of TG activity, inhibited basal and CCL19-stimulated migration of mature DCs. In agreement, FXIII-A-deficient DCs showed a reduced chemotactic response to CCL19. Consistent with these findings, CHO cells stably expressing human FXIII-A showed enhanced motility in transwell and scratch-wound assays. These cells displayed increased formation of membrane blebs, dynamic cell protrusions implicated in cell movement that were also observed in DCs. The results provide evidence suggesting that upregulation of cFXIII in DCs has a role in regulating cell motility.
Jayo
Asier
A
Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain.
Conde
Isabel
I
Lastres
Pedro
P
Jiménez-Yuste
Victor
V
González-Manchón
Consuelo
C
D000818:Animals; D016466:CHO Cells; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation; D002462:Cell Membrane / Q000648:ultrastructure; D002465:Cell Movement / Q000187:drug effects*; D054415:Chemokine CCL19 / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005176:Factor XIII / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
D054415:Chemokine CCL19; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D005176:Factor XIII; C008542:monodansylcadaverine; D002103:Cadaverine