Secretory pods can connect to the extracellular space. (A-B) Lanthanum was used as a tracer of extracellular spaces. Precipitates of lanthanum, which are present as opaque speckles (open arrowheads), have mixed with the content of the SP shown in this example. The SP appears to have fused with the plasmamembrane (black arrowhead). Scale bar represents 100 nm. (B) The SP in this example shows a funnel-shaped protrusion (open arrowhead) that is filled with lanthanum precipitate and connects to a WPB close by (WPBs are indicated with asterisks). The funnel-shaped structure may correspond to fused nanovesicles. Scale bar represents 100 nm. (C,C′,C″) Consecutive sections of 150-nm thickness, through an SP that in panel C″ opens up into the extracellular space via an omega-shaped figure. The SP is in contact with a WPB (white asterisk in panel C) and displays a clathrin-coated pit (arrow in C). Scale bar represents 1 μm. (D-D‴) Consecutive sections through 2 SPs (open arrowheads). In panel D‴, the SP at the top is surrounded by only a small rim of the cell surface, suggesting that the plasma membrane forms an elevation around the exit site, that is, secretion pore, of the SP. Scale bar represents 500 nm. (E,E′,E″,E‴) Consecutive sections through a secretory pod (black arrowhead in panel E) in a HUVEC that was secretagogue-challenged in the presence of anti-VWF antibodies to generate electron-dense globules of VWF (open arrowhead). The position of the SP in panel E is indicated in the consecutive sections E′ through E‴. Note that the VWF globules emanate from the SP. Scale bar represents 1 μm. (F) Enlargement of the SP shown in panel E. Scale bar represents 500 nm. (C-C″,E-F) The small speckles in panels C to C″ and panels E and F represent gold particles used as fiducial markers for electron tomography. Electron micrographs and tilt series were acquired with an FEI Tecnai 12 TEM at 120 kV and using an FEI Eagle 4kx4k CCD camera.