A Nerve and Mast Cell Sentinel System Releases Extracellular Condensates to Induce Macrophage Repair

ABSTRACT: The peritoneal cavity has a higher density of immune cells then does blood. These cells are primarily localized within the bulk flow of fluid. As such, any perturbation within the peritoneum, ranging from a sterile injury to endometriosis to ovarian cancer, requires that the immune cells find a way to recognize and nucleate at the site. Due to the very stochastic nature of the bulk flow within the peritoneal cavity, chemotactic gradients are unlikely to form and immune cell recruitment almost certainly requires a series of molecular events unlike in any other compartment. Herein, without breaching the peritoneal cavity we induced a laser injury, killing approximately a hundred mesothelial cells and used a two-photon microscope that could image through the abdominal wall to observe a spectacular accumulation of large peritoneal macrophages at the injury site. Large (1 μm) condensates (membraneless organelles) were released from mast cells due to sensory neuron activation and substance P release. The condensates expressed the scavenger receptor MARCO and harbored more than 200 different proteins. They were stable in extracellular fluid and highly adhesive causing macrophages to aggregate, nucleate and become M2-like at the injury site. Lattice light sheet microscopy unveiled mast cells to have very thin (<10nm) tentacle like filapodia (arms) that were often hundreds of microns in length, motile and grabbed the condensates from the mast cell surface and deposited them on neighboring cells thereby regulating the sphere of influence of each individual mast cell.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Peritoneal Fluid

SUBMITTER: Daniel Young  

LAB HEAD: Antoine Dufour

PROVIDER: PXD061150 | Pride | 2026-06-17

REPOSITORIES: Pride