Sub-endothelial platelet activation amplifies neutrophil transmigration within venular walls

Authors

Cimen, T., Fernandes Manchope, M., Klinkenberg, L., Goeb, V., Hoffmann Salles Bianchini, B., Reglero-Real, N., Kastenmueller, W., Alon, R., Nieswandt, B., Stegner, D., Girbl-Huemer, T.

Abstract

Neutrophil recruitment into inflamed tissues requires coordinated transmigration across the multilayered venular wall, yet how this process is regulated beyond the endothelium remains poorly understood. Here, we identify a previously unrecognized platelet-neutrophil circuit that controls this post-endothelial phase. Intravital microscopy of inflamed cremasteric venules showed that pioneer neutrophil transmigration enabled platelet entry into the sub-endothelial compartment of venular walls. There, platelets became activated and released CXCL7 in a GPVI- and GPIb-dependent manner, generating spatially confined chemokine microdomains. These platelet-derived cues directed follower neutrophil migration and promoted their exit across the pericyte layer into the interstitial tissue. Collectively, these findings identify extraluminal platelets as spatial organizers of neutrophil trafficking and uncover a localized intramural feedback mechanism in which neutrophils amplify their own recruitment within venular walls.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 25 Jul 2026.

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