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Angiogenesis Aug 2023Angiogenesis, barriergenesis, and immune cell migration are all key physiological events that are dependent on the functional characteristics of the vascular... (Review)
Review
Angiogenesis, barriergenesis, and immune cell migration are all key physiological events that are dependent on the functional characteristics of the vascular endothelium. The protein family of Nectins and Nectin-like molecules (Necls) is a group of cell adhesion molecules that are widely expressed by different endothelial cell types. The family includes four Nectins (Nectin-1 to -4) and five Necls (Necl-1 to -5) that either interact with each other by forming homo- and heterotypical interactions or bind to ligands expressed within the immune system. Nectin and Necl proteins are mainly described to play a role in cancer immunology and in the development of the nervous system. However, Nectins and Necls are underestimated players in the formation of blood vessels, their barrier properties, and in guiding transendothelial migration of leukocytes. This review summarizes their role in supporting the endothelial barrier through their function in angiogenesis, cell-cell junction formation, and immune cell migration. In addition, this review provides a detailed overview of the expression patterns of Nectins and Necls in the vascular endothelium.
Topics: Nectins; Cell Adhesion Molecules; Cell Movement; Transendothelial and Transepithelial Migration; Cell Adhesion
PubMed: 36867287
DOI: 10.1007/s10456-023-09871-y -
Biomedicine & Pharmacotherapy =... Jul 2020Post-stroke neural damage is a serious health concern which does not yet have an effective treatment. We have shown previously that Shuxuening injection (SXNI), a Ginkgo...
Shuxuening injection facilitates neurofunctional recovery via down-regulation of G-CSF-mediated granulocyte adhesion and diapedesis pathway in a subacute stroke mouse model.
Post-stroke neural damage is a serious health concern which does not yet have an effective treatment. We have shown previously that Shuxuening injection (SXNI), a Ginkgo biloba extract-based natural medicine, protects brain after an acute ischemic stroke, but its efficacy for post-stroke recovery is not known. This study was to investigate whether SXNI can improve the prognosis of stroke at a subacute phase. Mice with cerebral ischemia-reperfusion injury (CIRI) were established by middle cerebral artery occlusion (MCAO), and drugs or saline were injected by the tail vein every 12 h after reperfusion. The therapeutic effect of SXNI was evaluated by survival rate, modified neurologic severity scores (mNSS), open-field test, locomotive gait patterns, cerebral infarction volume, brain edema and histopathological changes. Subsequently, a combined method of RNA-seq and Ingenuity® Pathway Analysis (IPA) was performed to identify key targets and pathways of SXNI facilitating the prognosis of stroke in mouse brain. The results of the transcriptome analysis were verified by real time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), western blot (WB) and immunohistochemistry (IHC). The experimental results showed that in the new subacute stroke model, SXNI markedly improves the survival rate, neurological and motor functions and histopathological changes, and significantly reduces cerebral infarction and edema volume. RNA-seq analysis of subacute stroke mice with or without SXNI (3 mL/kg) indicated 963 differentially expressed genes (DEGs) with a fold change ≥ 1.5 and a P-value ≤ 0.01. IPA analysis of DEGs showed that granulocyte adhesion and diapedesis ranked first in the pathway ranking, and the most critical gene regulated by SXNI was G-csf. Simultaneously, RT-PCR, ELISA, WB and IHC results demonstrated that SXNI not only obviously reduced the mRNA expression levels of key genes G-csf, Sele and Mac-1 in this pathway, but also significantly decreased the protein expression levels of G-CSF in serum and E-selectin and MAC-1 in brain tissues. In summary, our research suggested that SXNI can exert a remarkable neurofunctional therapeutic effect on stroke mice via down-regulating G-CSF to inhibit granulocyte adhesion and diapedesis. This study provides experimental evidence that SXNI may fulfill the need for stroke medicine targeting specifically at the recovery stage.
Topics: Animals; Brain Ischemia; Disease Models, Animal; Down-Regulation; Drugs, Chinese Herbal; Granulocyte Colony-Stimulating Factor; Granulocytes; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred C57BL; Reperfusion Injury; Stroke; Transendothelial and Transepithelial Migration
PubMed: 32417690
DOI: 10.1016/j.biopha.2020.110213 -
European Journal of Immunology Feb 2012A major focus of researchers studying leukocyte recruitment has been to identify and understand how cell surface endothelial adhesion molecules, cell-to-cell junctional...
A major focus of researchers studying leukocyte recruitment has been to identify and understand how cell surface endothelial adhesion molecules, cell-to-cell junctional protein complexes, secreted chemokines and chemoattractants, and the vessel basement membrane structure organization coordinate the process of leukocyte recruitment. As research expands beyond the components initially identified as being necessary for leukocyte recruitment, attention has turned to the structures that regulate endothelial cell-to-matrix adhesion. In this issue of the European Journal of Immunology, Parsons et al. [Eur. J. Immunol. 2012. 42: 436-446] identify new players in the regulation of neutrophil diapedesis (transendothelial migration), namely the focal adhesion proteins, paxillin and focal adhesion kinase (FAK). While understudied, and indeed previously underappreciated, in leukocyte diapedesis, this Commentary discusses how the work by Parsons et al. implicates FAK and paxillin in the proximal (leukocyte rolling) and distal (diapedesis) steps of the multistep adhesion cascade of leukocyte recruitment.
Topics: Endothelium; Focal Adhesion Protein-Tyrosine Kinases; Humans; Neutrophils; Paxillin; Transendothelial and Transepithelial Migration
PubMed: 22266717
DOI: 10.1002/eji.201142342 -
Langmuir : the ACS Journal of Surfaces... May 2022Nanoparticle-based delivery of therapeutics to the brain has had limited clinical impact due to challenges crossing the blood-brain barrier (BBB). Certain cells, such as...
Nanoparticle-based delivery of therapeutics to the brain has had limited clinical impact due to challenges crossing the blood-brain barrier (BBB). Certain cells, such as monocytes, possess the ability to migrate across the BBB, making them attractive candidates for cell-based brain delivery strategies. In this work, we explore nanoparticle design parameters that impact both monocyte association and monocyte-mediated BBB transport. We use electrohydrodynamic jetting to prepare nanoparticles of varying sizes, compositions, and elasticity to address their impact on uptake by THP-1 monocytes and permeation across the BBB. An human BBB model is developed using human cerebral microvascular endothelial cells (hCMEC/D3) for the assessment of migration. We compare monocyte uptake of both polymeric and synthetic protein nanoparticles (SPNPs) of various sizes, as well as their effect on cell migration. SPNPs (human serum albumin/HSA or human transferrin/TF) are shown to promote increased monocyte-mediated transport across the BBB over polymeric nanoparticles. TF SPNPs (200 nm) associate readily, with an average uptake of 138 particles/cell. Nanoparticle loading is shown to influence the migration of THP-1 monocytes. The migration of monocytes loaded with 200 nm TF and 200 nm HSA SPNPs was 2.3-fold and 2.1-fold higher than that of an untreated control. RNA-seq analysis after TF SPNP treatment suggests that the upregulation of several migration genes may be implicated in increased monocyte migration (ex. integrin subunits α M and α L). Integrin β 2 chain combines with either integrin subunit α M chain or integrin subunit α L chain to form macrophage antigen 1 and lymphocyte function-associated antigen 1 integrins. Both products play a pivotal role in the transendothelial migration cascade. Our findings highlight the potential of SPNPs as drug and/or gene delivery platforms for monocyte-mediated BBB transport, especially where conventional polymer nanoparticles are ineffective or otherwise not desirable.
Topics: Endothelial Cells; Humans; Integrins; Monocytes; Nanoparticles; Transendothelial and Transepithelial Migration; Transferrin
PubMed: 35446569
DOI: 10.1021/acs.langmuir.2c00200 -
Frontiers in Immunology 2018Cell migration is indispensable for various biological processes including angiogenesis, wound healing, and immunity. In general, there are two different migration modes... (Review)
Review
Cell migration is indispensable for various biological processes including angiogenesis, wound healing, and immunity. In general, there are two different migration modes described, the mesenchymal migration mode and the amoeboid migration mode. Neutrophils rapidly migrate toward the sites of injury, infection, and inflammation using the amoeboid migration mode which is characterized by cell polarization and a high migration velocity. During site-directed trafficking of neutrophils from the blood stream into the inflamed tissue, neutrophils must first withstand shear stress while migrating on the 2-dimensional endothelial surface. Subsequently, they have to cross different physical barriers during the extravasation process including the squeezing through the compact endothelial monolayer that comprises the blood vessel, the underlining basement membrane and then the 3-dimensional meshwork of extracellular matrix (ECM) proteins in the tissue. Therefore, neutrophils have to rapidly switch between distinct migration modes such as intraluminal crawling, transmigration, and interstitial migration to pass these different confinements and mechanical barriers. The nucleus is the largest and stiffest organelle in every cell and is therefore the key cellular element involved in cellular migration through variable confinements. This review highlights the importance of nuclear deformation during neutrophil crossing of such confinements, with a focus on transendothelial migration and interstitial migration. We discuss the key molecular components involved in the nuclear shape changes that underlie neutrophil motility and squeezing through cellular and ECM barriers. Understanding the precise molecular mechanisms that orchestrate these distinct neutrophil migration modes introduces an opportunity to develop new therapeutic concepts for controlling pathological neutrophil-driven inflammation.
Topics: Animals; Cell Nucleus; Cellular Microenvironment; Humans; Immunity, Innate; Inflammation; Mice; Neutrophils; Nuclear Envelope; Pseudopodia; Receptors, Cytoplasmic and Nuclear; Transendothelial and Transepithelial Migration; Lamin B Receptor
PubMed: 30505310
DOI: 10.3389/fimmu.2018.02680 -
Blood Dec 2017Traditionally, in vitro flow chamber experiments and in vivo arterial thrombosis studies have been proved to be of vital importance to elucidate the mechanisms of... (Review)
Review
Traditionally, in vitro flow chamber experiments and in vivo arterial thrombosis studies have been proved to be of vital importance to elucidate the mechanisms of platelet thrombus formation after vessel wall injury. In recent years, it has become clear that platelets also act as modulators of inflammatory processes, such as atherosclerosis. A key element herein is the complex cross talk between platelets, the coagulation system, leukocytes, and the activated endothelium. This review provides insight into the platelet-endothelial interface, based on in vitro flow chamber studies and cross referenced with in vivo thrombosis studies. The main mechanisms of platelet interaction with the activated endothelium encompass (1) platelet rolling via interaction of platelet glycoprotein Ib-IX-V with endothelial-released von Willebrand factor with a supporting role for the P-selectin/P-selectin glycoprotein ligand 1 axis, followed by (2) firm platelet adhesion to the endothelium via interaction of platelet αβ with endothelial αβ and intercellular adhesion molecule 1, and (3) a stimulatory role for thrombin, the thrombospondin-1/CD36 axis and cyclooxygenase 1 in subsequent platelet activation and stable thrombus formation. In addition, the molecular mechanisms underlying the stimulatory effect of platelets on leukocyte transendothelial migration, a key mediator of atheroprogression, are discussed. Throughout the review, emphasis is placed on recommendations for setting up, reporting, interpreting, and comparing endothelial-lined flow chamber studies and suggestions for future studies.
Topics: Blood Platelets; Cell Communication; Endothelium, Vascular; Humans; Microfluidics; Receptor Cross-Talk; Transendothelial and Transepithelial Migration
PubMed: 29018081
DOI: 10.1182/blood-2017-04-780825 -
Annals of Biomedical Engineering Apr 2012Dendritic cells (DCs) are crucial components of the immune response, strategically positioned as immune sentinels. Complex trafficking and accurate positioning of DCs... (Review)
Review
Dendritic cells (DCs) are crucial components of the immune response, strategically positioned as immune sentinels. Complex trafficking and accurate positioning of DCs are indispensable for both immunity and tolerance. This is particularly evident for their therapeutic application where an unmet clinical need exists for DCs with improved migratory capacity upon adoptive transfer into patients. One critical step that directs the trafficking of DCs throughout the body is their egress from the vasculature, starting with their adhesive interactions with vascular endothelium under shear flow. Both tethering and rolling rely on interactions mediated by specific glycans attached to glycoproteins and glycolipids present on the DC surface. In DCs, surface glycosylation, including the expression of selectin ligands, changes significantly depending on the local microenvironment and the functional state of the cells. These changes have been documented and have potential implications in important cell functions such as migration. In this article, we review the glycobiological aspects in the context of DC interaction with endothelium, and offer insights on how it can be applied to modulate DC applicability in therapy.
Topics: Adoptive Transfer; Animals; Carbohydrate Metabolism; Dendritic Cells; Endothelium, Vascular; Glycosylation; Humans; Transendothelial and Transepithelial Migration
PubMed: 22045510
DOI: 10.1007/s10439-011-0448-5 -
Journal of Biomechanics May 2021During cancer metastasis, tumor cells undergo significant deformation in order to traverse through endothelial cell junctions in the walls of blood vessels. As cells...
During cancer metastasis, tumor cells undergo significant deformation in order to traverse through endothelial cell junctions in the walls of blood vessels. As cells pass through narrow gaps, smaller than the nuclear diameter, the spatial configuration of chromatin must change along with the distribution of nuclear enzymes. Nuclear stiffness is an important determinant of the ability of cells to undergo transendothelial migration, yet no studies have been conducted to assess whether tumor cell cytoskeletal or nuclear stiffness changes during this critical process in order to facilitate passage. To address this question, we employed two non-contact methods, Brillouin confocal microscopy (BCM) and confocal reflectance quantitative phase microscopy (QPM), to track the changes in mechanical properties of live, transmigrating tumor cells in an in vitro collagen gel platform. Using these two imaging modalities to study transmigrating MDA-MB-231, A549, and A375 cells, we found that both the cells and their nuclei soften upon extravasation and that the nuclear membranes remain soft for at least 24 h. These new data suggest that tumor cells adjust their mechanical properties in order to facilitate extravasation.
Topics: Cell Line, Tumor; Cell Movement; Cell Nucleus; Collagen; Humans; Microscopy, Confocal; Neoplasms; Transendothelial and Transepithelial Migration
PubMed: 33882444
DOI: 10.1016/j.jbiomech.2021.110400 -
Viruses Aug 2021A small fraction of HIV-1-infected T cells forms populations of latently infected cells when they are a naive T-cell subset or in transit to a resting memory state....
A small fraction of HIV-1-infected T cells forms populations of latently infected cells when they are a naive T-cell subset or in transit to a resting memory state. Latently HIV-1-infected cells reside in lymphoid tissues and serve as viral reservoirs. However, whether they systemically recirculate in the body and re-enter the lymphoid nodes are unknown. Here, we employed two in-vitro cell coculture systems mimicking the lymphatic endothelium in lymph nodes and investigated the homing potential, specifically the transendothelial migration (TEM), of two latently HIV-1-infected cell lines (J1.1 and ACH-2). In trans-well coculture systems, J1.1 and ACH-2 showed higher TEM efficiencies than their parental uninfected and acutely infected cells. The efficiency of TEM was enhanced by the presence of stromal cells, such as HS-5 and fibroblastic reticular cells. In an in-vitro reconstituted, three-dimensional coculture system in which stromal cells are embedded in collagen matrices, J1.1 showed slightly higher TEM efficiency in the presence of HS-5. In accordance with these phenotypes, latently infected cells adhered to the endothelial cells more efficiently than uninfected cells. Together, our study showed that latently HIV-1-infected cells enhanced cell adhesion and TEM abilities, suggesting their potential for efficient homing to lymph nodes.
Topics: CD4-Positive T-Lymphocytes; Cell Line; Coculture Techniques; Endothelial Cells; HIV-1; Humans; Receptors, Lymphocyte Homing; Transendothelial and Transepithelial Migration; Virus Activation; Virus Latency
PubMed: 34452453
DOI: 10.3390/v13081589 -
Bio-medical Materials and Engineering 2017Thanks to their immune properties, the mesenchymal stem cells (MSC) are a promising source for cell therapy. Current clinical trials show that MSC administrated to... (Review)
Review
Thanks to their immune properties, the mesenchymal stem cells (MSC) are a promising source for cell therapy. Current clinical trials show that MSC administrated to patients can treat different diseases (graft-versus-host disease (GVHD), liver cirrhosis, systemic lupus, erythematosus, rheumatoid arthritis, type I diabetes…). In this case, the most common mode of cell administration is the intravenous injection, and the hemodynamic environment of cells induced by blood circulation could interfere on their behavior during the migration and homing towards the injured site. After a brief review of the mechanobiology concept, this paper will help in understanding how the mechanical environment could interact with MSC behavior once they are injected to patient in cell-based treatment.
Topics: Animals; Biomechanical Phenomena; Biophysics; Cell Movement; Chemotaxis; Hemodynamics; Humans; Injections, Intravenous; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Transendothelial and Transepithelial Migration
PubMed: 28372277
DOI: 10.3233/BME-171623