Noninvasive assessment of localized inflammatory responses

Abstract

Inflammatory diseases are associated with the accumulation of activated inflammatory cells, particularly polymorphonuclear neutrophils (PMN), which release reactive oxygen species (ROS) to eradicate foreign bodies and microorganisms. To assess the location and extent of localized inflammatory responses, L-012, a highly-sensitive chemiluminescence probe, was employed to non-invasively monitor the production of ROS. We find that L-012-associated chemiluminescence imaging can be used to identify and to quantify the extent of inflammatory responses. Furthermore, regardless of differences among animal models, there is a good linear relationship between chemiluminescence intensity and PMN numbers surrounding inflamed tissue. Depletion of PMN substantially diminished L-012-associated chemiluminescence in vivo. Finally, L-012-associated chemiluminescence imaging was found to be a powerful tool for assessing implant-mediated inflammatory responses by measuring chemiluminescent intensities at the implantation sites. These results support the use of L-012 for monitoring the kinetics of inflammatory responses in vivo via the detection and quantification of ROS production.

In Vivo Imaging of Reactive Oxygen and Nitrogen Species in Murine Colitis

“…43 These studies model a disease at or near the skin of the mouse enabling sensitive detection without need of deep tissue penetrance. In vivo chemiluminescence imaging of internal organs is more challenging, but has been shown successful in our study, and after lipopolysaccharide injection, 31 correlating with abdominal location of an NF-kB luciferin reporter in a systemic lupus model 45 and in models of the liver and intra-abdominal sepsis.…”

“…This is necessary to consider because L-012 reacts with RONS very quickly, signal strength decrease within 30 minutes, 31,43 and high variations between mice are common and expected in in vivo settings. Instead of the chemiluminescent signals in abdominal region measured at 4 minutes after L-012 injection (Fig.…”

Non-invasive Characterization of Immune Responses to Biomedical Implants

“…50 In another investigation, L-012, a luminol-derivative chemiluminescence probe with higher sensitivity toward ROS, has been employed to image ROS activity in vivo using various inflammation and inflection models including allergy-and biomaterialmediated inflammatory responses. 113 Most recently, L-012 was used to determine the extent of biomaterialmediated ROS production in vivo. Interestingly, it was found that chemiluminescence signal was strongly dependent on type of biomaterial.…”

“…3a and 3b). 113 These studies reveal that chemiluminescence of ROS generation is a promising modality for characterizing the biocompatibility and pro-inflammatory property of biomaterials and medical implants.…”

“…(a) L-012 probe was used to assess the degree of ROS generation by various implants; (b) A good linear relationship was seen between number of recruited PMNs and ROSassociated chemiluminescence intensity at various implant sites. Adapted from Zhou et al113 (c) Ratiometric pH probes were used to measure the extent of tissue acidosis triggered by various implant biomaterials; (d) The extent of tissue acidosis (pH change) and inflammatory cell accumulation at the implant sites showed a good relationship. Abbreviations for particles made of different materials-PEG (polyethylene glycol); PLA (poly-L-lactic acid); PNIPAM-NH 2 (amine-rich poly-N-isopropylacrylamide-co-N-(3-aminopropyl) methacryl-amide); PS (polystyrene); SiO 2 (silicone dioxide).…”