Leukocyte recruitment during inflammation and angiogenesis

Time period: 2013-01-01 to 2017-12-31

Project leader: Mia Phillipson

Funder: Ragnar Söderberg Foundation

Type of award: Project grant

Total fundning: 8 000 000 SEK

Detrimental inflammation contributes to a majority of diseases, and increased knowledge of the mechanisms that regulate leukocyte recruitment is central to limit inflammatory response. We previously established a new step in the leukocyte recruitment cascade, namely intravascular crawling on endothelium to transmigration sites. We now study the information exchanged between leukocytes and underlying endothelial cells, which result in efficient leukocyte emigration. Interestingly, we recently found that leukocytes were recruited to focal hypoxia and were essential for restoration of the intra-islet vasculature observed in experimental and clinical transplantation of insulin-producing pancreatic islets to muscle. We aim at determining the cue for recruitment of these pro-angiogenic leukocytes to hypoxia, their identity and role in angiogenesis as well as adhesion molecules involved, in addition to continue our studies of leukocyte recruitment during inflammation. By employing state of the art techniques for studies of leukocyte-endothelial crosstalk in vivo (high speed in vivo confocal and intravital microscopy) and our established methods (leukocyte recruitment, experimental islet transplantation and muscle ischemia), we intend to delineate future targets for development of anti-inflammatory drugs as well as means to stimulate or inhibit angiogenesis. Translation of obtained findings is facilitated by collaboration within the Nordic Network for Clinical Islet Transplantation.