title: A dynamic real time in vivo and static ex vivo analysis of granulomonocytic cell migration in the collagen-induced arthritis model.
abstract: Neutrophilic granulocytes and monocytes (granulomonocytic cells; GMC) drive the inflammatory process at the earliest stages of rheumatoid arthritis (RA). The migratory behavior and functional properties of GMC within the synovial tissue are, however, only incompletely characterized. Here we have analyzed GMC in the murine collagen-induced arthritis (CIA) model of RA using multi-photon real time in vivo microscopy together with ex vivo analysis of GMC in tissue sections.GMC were abundant as soon as clinical arthritis was apparent. GMC were motile and migrated randomly through the synovial tissue. In addition, we observed the frequent formation of cell clusters consisting of both neutrophilic granulocytes and monocytes that actively contributed to the inflammatory process of arthritis. Treatment of animals with a single dose of prednisolone reduced the mean velocity of cell migration and diminished the overall immigration of GMC.In summary, our study shows that the combined application of real time in vivo microscopy together with elaborate static post-mortem analysis of GMC enables the description of dynamic migratory characteristics of GMC together with their precise location in a complex anatomical environment. Moreover, this approach is sensitive enough to detect subtle therapeutic effects within a very short period of time.
authors.affiliation: Divison of Rheumatology, Internal Medicine III, Medical University of Vienna, Waehringer Guertel, Vienna, Austria.
authors.forename: Ruth
authors.initials: R
authors.lastname: Byrne
authors.forename: Eva
authors.initials: E
authors.lastname: Rath
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Hladik
authors.forename: Birgit
authors.initials: B
authors.lastname: Niederreiter
authors.forename: Michael
authors.initials: M
authors.lastname: Bonelli
authors.forename: Sophie
authors.initials: S
authors.lastname: Frantal
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Clemens
authors.initials: C
authors.lastname: Scheinecker
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000175:diagnosis*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D009000:Monocytes / Q000187:drug effects / Q000473:pathology*; D011239:Prednisolone / Q000494:pharmacology; D013583:Synovial Membrane / Q000473:pathology; D013997:Time Factors
chemical_list: D011239:Prednisolone