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.
Highlights
Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by chronic articular inflammation and progressive destruction of the joints
We found that the average cell migration speed of GMC through a predefined region of interest (ROI) was significantly decreased in collagen-induced arthritis (CIA) animals (2.7561.17 mm/min) as compared to the rare cells we could visualize in the joints of healthy controls (3.1161.51 mm/min; p,0.001) (Figure 2B, Movie S1, and Movie S2), suggesting that in healthy animals cells were trafficking accidentally through the joint, while in arthritic mice cells were more engaged within the joint tissue
We found that analysis of GMC clusters at higher magnification over time revealed that both EGFPhigh granulocytes and EGFPlow monocytes are involved in the formation of cell clusters (Figure 3B and Movie S4)
Summary
Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by chronic articular inflammation and progressive destruction of the joints. The synovial tissue in inflamed joints is infiltrated with a broad variety of immune cells with different functional roles in the pathogenesis of the disease. Their presumed cognate or non-cognate interactions may result in the formation of cell clusters and even lymphoid follicle-like structures. Key features of the behavior and properties of GMC, such as the dynamics of cell immigration and migration within inflamed joint tissues and spatiotemporal aspects of the functional activities of these cells in such tissue sites, have not been well described to date [6,7], leaving important gaps in our understanding of the inflammatory process
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
