52 - Communication libre
Transplantation and regeneration
3 juin 2021, 13:50 - 15:20, Stream 4: Video Invited, SST, SSCViscérale & ARS
Primordial GATA6 macrophages function as extravascular platelets in sterile injury
J. Zindel1, M. Peiseler2, C. Deppermann2, W.-Y. Lee2, J. Deniset2, B. Surewaard2, P. Kubes2, D. Candinas1, Presenter: J. Zindel1 (1Bern, 2Calgary)
Abdominal surgeries are life-saving operations. However, some patients develop intra-abdominal scars called peritoneal adhesions. Peritoneal adhesions cause significant morbidity and generate a significant burden for health care systems. The mechanism of adhesion formation is poorly understood and up to date no specific treatment exists. Here we ask the question how peritoneal macrophages contribute towards post-surgical wound healing and adhesion formation. Mechanistically, we sought to explore how cavity macrophages that are suspended in the fluid phase (peritoneal fluid) can identify injury and how they migrate towards it.
We use intravital microscopy, a method that allows to dynamically observe cellular movements in vivo. To study the migration patterns of peritoneal macrophages we developed a novel imaging technique that allows to image within the peritoneal cavity through the intact abdominal wall by using multi-photon excitation and a highly-sensitive non-descanned detection system.
We show that cavity macrophages that are suspended in peritoneal fluid, rapidly form thrombus-like structures in response to injury. We show how the aggregates that form in response to injury physically sealed injuries and promoted rapid repair of focal lesions. In these focal lesions, macrophage aggregation was tightly controlled and the aggregate size did not increase indefinitely. In response to extensive iatrogenic injuries, such as surgical situations, the aggregate formation did not stop, resulting in huge super-aggregates that served as a scaffold for the fibrotic growth of peritoneal adhesions.
Peritoneal macrophages promote healing of focal types of perturbations, a type of injury that we hypothesize the immune system has been challenged with throughout evolution. However, iatrogenic procedures such as abdominal surgery, which include exposure to the external environment and potential implantation of foreign material, reflect a type of injury that appears to have no evolutionary precedent. In this scenario, peritoneal macrophages may cause detrimental scarring (adhesions) in an inadvertent attempt to repair tissue. Thus, the inhibition of macrophage aggregation may provide a target to prevent adhesion formation after surgery in the peritoneal cavity and perhaps other cavities that contain these cells.