MCs release insoluble heparin-containing particles. (A) SEM of an unstimulated rat peritoneal MC (rPMC). Bar, 2 µm. (B) SEM of rPMC 15 min after treatment with compound 48/80 at 5 µg/ml. Bar, 2 µm. (C) SEM of a single extracellular granule. Bar, 500 nm. Release of particles by rat peritoneal MCs was observed repeatedly (in greater than three independent experiments). SEMs are shown from one representative experiment. For some trials (A–C), lavage was pooled from multiple rats to obtain sufficient material for analysis. (D) Confocal micrograph of MCs in mouse footpad (granule heparin labeled with Alexa Fluor 488–conjugated avidin) 30 min after PBS injection showing undegranulated MCs. Bar, 30 µm. (E) Mouse footpad MCs surrounded by extracellular particles 30 min after injection of 5 µg of compound 48/80. Bar, 30 µm. Release of particles in vivo was observed in greater than three independent experiments using groups of two to three mice each. Experiments are representative of data derived from greater than three animals.