Locomotion of monocytes on endothelium is a critical step during extravasation

Schenkel, Alan R.; Mamdouh, Zahra; Müller, William A.

doi:10.1038/ni1051

Cited by 385 publications

(377 citation statements)

References 36 publications

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“…7 and data not shown) reveals that CD99-blocked PMN are in fact not firmly arrested, but moving dynamically within EC junctions, sometimes back and forth along the same junctional space as if looking for a place to transmigrate. This is reminiscent of the appearance of monocytes blocked on TEM by anti-PECAM, which "walked" along the tops of the EC borders (10). The live imaging illustrates the capacity of the neutrophil to deform the membrane of the EC to accommodate its movement (data not shown).…”

Section: Discussionmentioning

confidence: 90%

“…Several members of the JAM family have been implicated in transmigration. Several reports suggest JAM-A mediates TEM of leukocytes (41,42), although the transmigration of human neutrophils (11) and monocytes (10) in vitro is unaffected by anti-JAM-A mAb. JAM-B and -C have been implicated in leukocyte extravasation in vitro and in vivo (43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

“…This causes arrest of leukocytes on the endothelial surface. The leukocyte moves from the site of firm adhesion to the nearest junction in a newly identified step termed locomotion, which is mediated by the ␤ 2 integrins and their counterreceptors ICAM-1 and ICAM-2 (10). Indeed, LFA-1 and ICAM-1 remain tightly apposed during the subsequent transmigration step (11).…”

Section: Cd99 Is a Keymentioning

confidence: 99%

“…Neutrophils were added to HUVEC cultured to confluency atop collagen gels set into 30-mm tissue culture dishes with glass coverslip bottoms (10). Interactions between neutrophils and EC were visualized by time-lapse photography using a Zeiss Axiovert 200M widefield microscope.…”

Section: Live Imaging Of Pmn Tem Under Static Conditionsmentioning

confidence: 99%

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CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

Lou

Alcaide

Luscinskas

et al. 2007

The Journal of Immunology

157

145

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Transendothelial migration of leukocytes is a critical event for inflammation, but the molecular regulation of this event is only beginning to be understood. PECAM (CD31) is a major mediator of monocyte and neutrophil transmigration, and CD99 was recently defined as a second mediator of the transmigration of monocytes. Expression of CD99 on the surface of circulating polymorphonuclear cells (PMN) is low compared with expression of CD99 on monocytes or expression of PECAM on PMN. We demonstrate here that, despite low expression of CD99, Fab of Abs against CD99 blocked over 80% of human neutrophils from transmigrating across HUVEC monolayers in an in vitro model of inflammation. Blocking CD99 on either the neutrophil or endothelial cell side resulted in a quantitatively equivalent block, suggesting a homophilic interaction between CD99 on the neutrophil and CD99 on the endothelial cell. Blocking CD99 and PECAM together resulted in additive effects, suggesting the two molecules work at distinct steps. Confocal microscopy confirmed that CD99-blocked neutrophils lodged in endothelial cell junctions at locations distal to PECAM-blocked neutrophils. The CD99-blocked PMN exhibited dynamic lateral movement within endothelial cell junctions, indicating that only the diapedesis step was blocked by interference with CD99. Anti-CD99 mAb also blocked PMN transmigration in a second in vitro model that incorporated shear stress. Taken together, the evidence demonstrates that PECAM and CD99 regulate distinct, sequential steps in the transendothelial migration of neutrophils during inflammation.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Cd99 Is a Keymentioning

confidence: 99%

Section: Live Imaging Of Pmn Tem Under Static Conditionsmentioning

confidence: 99%

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CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

Lou

Alcaide

Luscinskas

et al. 2007

The Journal of Immunology

157

145

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“…Crawling was first observed in vitro and initially termed "locomotion": monocytes that adhered to HUVECs were found to actively move to cellular junctions to start transmigration within seconds (47). However, blocking of CD18, ICAM-1, or ICAM-2 rendered the monocytes unable to locate endothelial cell junctions and caused the cells to wander during 90 min without effectively initiating transmigration (47). Blockade of ICAM-1 and ICAM-2 still allowed movement of monocytes, whereas blockade of CD11a and CD11b resulted in immobile monocytes "pirouetting" on their uropod (47).…”

Section: Leukocyte Recruitmentmentioning

confidence: 99%

Integrin Regulation during Leukocyte Recruitment

Herter

Zarbock

2013

The Journal of Immunology

170

138

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Integrins are recognized as vital players in leukocyte recruitment. Integrin malfunction causes severe disease patterns characterized by the inability to fight pathogens. Although inflammatory reactions are beneficial and necessary for host defense, these reactions have to be controlled to prevent tissue destruction and harmful sequelae. In this review, we discuss the different signaling pathways leading to the change of integrin adhesiveness in neutrophils, monocytes, and lymphocytes. We thereby focus on the importance of integrin activation for the different steps of the leukocyte recruitment cascade, including rolling, adhesion, postadhesion strengthening, intravascular crawling, and transmigration, as each step necessitates the proper functioning of a distinct set of integrin molecules that has to be activated specifically. Additionally, we discuss endogenous mechanisms that balance and counteract integrin activation and limit leukocyte recruitment at the site of inflammation. Further insight into these complex mechanisms may provide new approaches for developing new anti-inflammatory therapies.

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Endothelial Cells: Immunological Aspects

Sumitran–Holgersson¹,

Holgersson

2010

Encyclopedia of Life Sciences

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It is now clear that the vascular endothelium is not merely a passive vessel wall lining but is actually a multifunctional organ involved in maintaining homeostasis. Strategically located at the interface between blood and the extravascular space, the endothelium is a highly specialised cellular system which plays a key role in physiological processes such as blood supply, nutrient delivery, metabolic homeostasis and immune cell trafficking, as well as pathological processes such as inflammation. Endothelial cells represent a highly heterogeneous population of cells with the ability to interact with and modulate the function of immune cells. These cells regulate the traffic and functions of leucocytes by expressing adhesion molecules and cytokines in a regulated way. The ability of endothelial cells (ECs) to recruit Ag‐specific T cells into the inflammatory sites by displaying cognate major histocompatibility complex (MHC)–peptide complexes contributes a new dimension to the central role played by endothelium in the regulation of immune responses. Key Concepts: Endothelial cells are not just an inert barrier between the blood and parenchyma. The morphology of the endothelial lining differs between vascular beds. The endothelial cell orchestrates cellular processes key to the inflammatory reaction. A regulated use of different adhesion molecules and chemokines guides tissue‐specific leucocyte extravasation. Selectin ligands are carbohydrates with a common structural motif, the tetrasaccharide sialyl‐Lewis X. Especially, microvascular endothelial cells can act as antigen‐presenting cells. Endothelial cells are both targets for and a source of cytokines – soluble polypeptides acting as mediators of communication with leucocytes and other cells.

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Locomotion of monocytes on endothelium is a critical step during extravasation

Cited by 385 publications

References 36 publications

CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

Integrin Regulation during Leukocyte Recruitment

Endothelial Cells: Immunological Aspects

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