A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them

By C. Carman, T. Springer. Journal of Cell Biology, 2004

705 citations recorded by the source corpus.

The basic route and mechanisms for leukocyte migration across the endothelium remain poorly defined. We provide definitive evidence for transcellular (i.e., through individual endothelial cells) diapedesis in vitro and demonstrate that virtually all, both para- and transcellular, diapedesis occurs in the context of a novel “cuplike” transmigratory structure. This endothelial structure was comprised of highly intercellular adhesion molecule-1– and vascular cell adhesion molecule-1–enriched vertical microvilli-like projections that surrounded transmigrating leukocytes and drove redistribution of their integrins into linear tracks oriented parallel to the direction of diapedesis. Disruption of projections was highly correlated with inhibition of transmigration. These findings suggest a novel mechanism, the “transmigratory cup”, by which the endothelium provides directional guidance to leukocytes for extravasation.

Subfields: Immunology, Immunology and Allergy, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/32f306fcf96ed098b4d4446b32cd9452048a25a6

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Citations in the corpus

Getting to the site of inflammation: the leukocyte adhesion cascade updated (2007, background): “Adherent leukocytes can induce the formation of 'docking structures' or 'transmigratory cups', which are endothelial-cell projections rich in ICAM1 and VCAM1 and cytoplasmic molecules such as ERM (ezrin, radixin and moesin) proteins and cytoskeletal components (such as vinculin, α-actinin and talin-”
Neutrophils, from marrow to microbes. (2010, background): “These cups are necessary for efficient transcellular migration both via the transcellular route and via the paracellular route (Carman and Springer, 2004).”
Reactive Oxygen Species in Inflammation and Tissue Injury (2014, neutral): “Transmigratory cups are microvilli-like projections that surround leukocytes and help in efficient transendothelial migration of leukocytes (24, 52).”
Mechanisms of Leukocyte Transendothelial Migration (2011, methodology): “The published in vitro studies of transcellular migration either used MCP-1, platelet activating factor, or SDF-1 to stimulate migration of monocytes, neutrophils, and T cells, respectively (10), or employed mitogen-activated T lymphoblasts (56, 87).”
The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction (2009, background): “Vesiculo-vacuolar organelles or caveolae have been suggested to be involved in regulating this transcellular diapedesis of leukocytes [86, 87].”
The blood-brain barrier in brain homeostasis and neurological diseases. (2009, neutral): “Moreover, preliminary results indicated that adhesion of breast carcinoma cells on cultured brain ECs induced the formation of actin-rich apical membrane protrusions (unpublished observations), similar to the trans-migratory cups underneath leukocytes known to mediate leukocyte diapedesis [154].”
ICAM-1 signaling in endothelial cells (2009, background): “the leukocytes’ transmigratory process and guide them via a paracellular or transcellular route [8, 9].”
The neutrophil in vascular inflammation (2011, background): “Endothelial cells are very active and responsive during transmigration and form docking structures (endothelial projections”
Pathophysiology of Atherosclerosis (2022, background): “On the other hand, in the transcellular route, cells migrate through the body of ECs; however, this type of transmigration has been observed in only 10–30% of the events in vitro [137,138].”
Ischemia/Reperfusion (2016, neutral): “myocardial infarction via use of lipoxygenase inhibitors or genetic ablation of 15-lipoxygenase (117, 392, 617, 618, 731, 811, 883).”
CNS immune privilege: hiding in plain sight (2006, background): “Lymphocyte transcellular migration occurs through recruitment of endothelial ICAM-1 to caveola- and F-actinrich domains.”
Immune cell migration in inflammation: present and future therapeutic targets (2005, background): “Both routes demonstrate a proactive function for both apical and junctional endothelial ICAM-1 and VCAM-1, whose expression is differentially increased at specific sites of inflammatio”