Description: During inflammation, leukocyte–endothelial cell interactions generate molecular signals that regulate cell functions. The Ca 2+ - and F-actin–binding leukocyte-specific protein 1 (LSP1) expressed in leukocytes and nonhematopoietic endothelial cells is pivotal in regulating microvascular permeability and leukocyte recruitment. However, cell-specific function of LSP1 during leukocyte recruitment remains elusive. Using intravital microscopy of cremasteric microvasculature of chimeric LSP1-deficient mice, we show that not neutrophil but endothelial LSP1 regulates neutrophil transendothelial migration and extravascular directionality without affecting the speed of neutrophil migration in tissue in response to CXCL2 chemokine gradient. The expression of PECAM-1–sensitive α 6 β 1 integrins on the surface of transmigrated neutrophils was blunted in mice deficient in endothelial LSP1. Functional blocking studies in vivo and in vitro elucidated that α 6 β 1 integrins orchestrated extravascular directionality but not the speed of neutrophil migration. In LSP1-deficient mice, PECAM-1 expression was reduced in endothelial cells, but not in neutrophils. Similarly, LSP1-targeted small interfering RNA silencing in murine endothelial cells mitigated mRNA and protein expression of PECAM-1, but not ICAM-1 or VCAM-1. Overexpression of LSP1 in endothelial cells upregulated PECAM-1 expression. Furthermore, the expression of transcription factor GATA-2 that regulates endothelial PECAM-1 expression was blunted in LSP1-deficient or LSP1-silenced endothelial cells. The present study unravels endothelial LSP1 as a novel cell-specific regulator of integrin α 6 β 1 -dependent neutrophil extravascular chemotactic function in vivo, effective through GATA-2–dependent transcriptional regulation of endothelial PECAM-1 expression.

Description: Aims Retention of low-density lipoprotein (LDL) cholesterol beneath the arterial endothelium initiates an inflammatory response culminating in atherosclerosis. Since the overlying endothelium is healthy and intact early on, it is likely that LDL passes through endothelial cells by transcytosis. However, technical challenges have made confirming this notion and elucidating the mechanisms of transcytosis difficult. We developed a novel assay for measuring LDL transcytosis in real time across coronary endothelial cell monolayers; we used this approach to identify the receptor involved. Methods and results Murine aortas were perfused ex vivo with LDL and dextran of a smaller molecular radius. LDL (but not dextran) accumulated under the endothelium, indicating that LDL transcytosis occurs in intact vessels. We then confirmed that LDL transcytosis occurs in vitro using human coronary artery endothelial cells. An assay was developed to quantify transcytosis of DiI-LDL in real time using total internal reflection fluorescence microscopy. DiI-LDL transcytosis was inhibited by excess unlabelled LDL, while degradation of the LDL receptor by PCSK9 had no effect. Instead, LDL colocalized partially with the scavenger receptor SR-BI and overexpression of SR-BI increased LDL transcytosis; knockdown by siRNA significantly reduced it. Excess HDL, the canonical SR-BI ligand, significantly decreased LDL transcytosis. Aortas from SR-BI -deficient mice were perfused ex vivo with LDL and accumulated significantly less sub-endothelial LDL compared with wild-type littermates. Conclusion We developed an assay to quantify LDL transcytosis across endothelial cells and discovered an unexpected role for SR-BI. Elucidating the mechanisms of LDL transcytosis may identify novel targets for the prevention or therapy of atherosclerosis.

Description: Obesity is associated with inflammation and immune cell recruitment to adipose tissue, muscle and intima of atherosclerotic blood vessels. Obesity and hyperlipidemia are also associated with tissue insulin resistance and can compromise insulin delivery to muscle. The muscle/fat microvascular endothelium mediates insulin delivery and facilitates monocyte transmigration, yet its contribution to the consequences of hyperlipidemia is poorly understood. Using primary endothelial cells from human adipose tissue microvasculature (HAMEC), we investigated the effects of physiological levels of fatty acids on endothelial inflammation and function. Expression of cytokines and adhesion molecules was measured by RT-qPCR. Signaling pathways were evaluated by pharmacological manipulation and immunoblotting. Surface expression of adhesion molecules was determined by immunohistochemistry. THP1 monocyte interaction with HAMEC was measured by cell adhesion and migration across transwells. Insulin transcytosis was measured by total internal reflection fluorescence microscopy. Palmitate, but not palmitoleate, elevated the expression of IL-6, IL-8, TLR2 (Toll-like receptor 2), and intercellular adhesion molecule 1 (ICAM-1). HAMEC had markedly low fatty acid uptake and oxidation, and CD36 inhibition did not reverse the palmitate-induced expression of adhesion molecules, suggesting that inflammation did not arise from palmitate uptake/metabolism. Instead, inhibition of TLR4 to NF-B signaling blunted palmitate-induced ICAM-1 expression. Importantly, palmitate-induced surface expression of ICAM-1 promoted monocyte binding and transmigration. Conversely, palmitate reduced insulin transcytosis, an effect reversed by TLR4 inhibition. In summary, palmitate activates inflammatory pathways in primary microvascular endothelial cells, impairing insulin transport and increasing monocyte transmigration. This behavior may contribute in vivo to reduced tissue insulin action and enhanced tissue infiltration by immune cells.

Description: Northwestern Namibia, at the landfall of the Walvis Ridge, was affected by the Tristan da Cunha mantle plume during continental rupture between Africa and South America, as evidenced by the presence of the Etendeka continental flood basalts. Here we use data from a passive-source seismological network to investigate the upper mantle structure and to elucidate the Cretaceous mantle plume-lithosphere interaction. Receiver functions reveal an interface associated with a negative velocity contrast within the lithosphere at an average depth of 80 km. We interpret this interface as the relic of the lithosphereasthenosphere boundary (LAB) formed during the Mesozoic by interaction of the Tristan da Cunha plume head with the pre-existing lithosphere. The velocity contrast might be explained by stagnated and ‘‘frozen’’ melts beneath an intensively depleted and dehydrated peridotitic mantle. The present-day LAB is poorly visible with converted waves, indicating a gradual impedance contrast. Beneath much of the study area, converted phases of the 410 and 660 km mantle transition zone discontinuities arrive 1.5 s earlier than in the landward plume-unaffected continental interior, suggesting high velocities in the upper mantle caused by a thick lithosphere. This indicates that after lithospheric thinning during continental breakup, the lithosphere has increased in thickness during the last 132 Myr. Thermal cooling of the continental lithosphere alone cannot produce the lithospheric thickness required here. We propose that the remnant plume material, which has a higher seismic velocity than the ambient mantle due to melt depletion and dehydration, significantly contributed to the thickening of the mantle lithosphere.

Description: We study the crustal and lithospheric mantle structure under central Betics in the westernmost Mediterranean region by migrating P-receiver functions along a dense seismic profile (∼2 km interstation distance). The profile, North–South oriented, probes the crustal structure of different geological units, from the Alboran domain in the south with metamorphic rocks, through the External Zones with sedimentary rocks to the Variscan terrains of the Iberian Massif in the north. From north to south, the Moho depth increases from ∼30 km to ∼46 km underneath the Guadix basin, due to the underthrusting of the Iberian crust below the Alboran crust, and suddenly shallows to ∼30 km underneath the Internal Zones with a step of 17 km. This sharp Moho step correlates well with a lithospheric step of ∼40 km, where the thickness of the lithosphere changes abruptly from ∼100 km in the north to ∼50 km in the south. We interpret this sharp and prominent lithospheric step as the termination of the Iberian lithosphere caused by a near-vertical STEP (Subduction-Transform-Edge-Propagator) fault that continues towards the surface as a positive flower tectonic structure of crustal scale. This STEP fault is located at the northern edge of the narrow Westernmost Mediterranean subduction system facilitating the slab rollback motion towards the west. The sharp termination of the Iberian lithosphere occurs under the contact between the Alpujarride and the Nevado-Filabride complexes of the Alboran domain in an ENE-WSW right-lateral transpressive shear zone. The thickest crust and lithosphere do not correlate with the highest topography along the profile suggesting that this high topography is a combined effect of the positive flower structure, and the push up of the asthenosphere produced by the removal of the Iberian lithosphere.

Description: The SWATH-D experiment is dense deployment of 154 seismic stations in the Central and Eastern Alps between Italy and Austria, complementing the larger-scale sparser AlpArray Seismic Network (AASN). SWATH-D will provide high resolution images from the surface into the upper mantle, and allow observations of local seismicity. SWATH-D focuses on a key area of the Alps where the hypothesized flip in subduction polarity has been suggested, and where an earlier seismic profile (TRANSALP) has imaged a jump in the Moho. Where mains power is available (at ca. 80 sites) stations are providing realtime data via the cellphone network and are equipped with Güralp CMG-3EPSC (60s) seismometers and Earth Data Recorders EDR-210. The rest of the stations are offline and consist mainly of Nanometrics Trillium Compact (120s) and Güralp CMG-3EPSC (60s) seismometers equipped with either Omnirecs CUBE3 or PR6-24 Earth Data Loggers. All stations are equipped with external GPS antennas and the sampling rate is 100 Hz (Heit, et al., 2018). The network will operate for 2 years starting in July 2017. The Swath-D data will be used directly by 20 individual proposals of the MB-4D Priority Program (Mountain Building Processes in Four Dimensions, 2017) of the German Research Foundation (DFG) and data products derived from it will contribute to additional 13 proposals. SWATH-D is thus an important link between the MB-4D Priority Program and the international AlpArray communities and a scientific service to many of the proposals within the DFG Priority Program. Waveform data are available from the GEOFON data centre, under network code ZS, and are embargoed until August 2023. After the end of embargo, data will be openly available under CC-BY 4.0 license according to GIPP-rules.

Description: A seismological network was operated at the junction of the aseismic Walvis Ridge with the northwestern Namibian coast. We mapped crustal thickness and bulk Vp/Vs ratio by the H‐k analysis of receiver functions. In the Damara Belt, the crustal thickness is ~35 km with a Vp/Vs ratio of 〈1.75. The crust is ~30 km thick at the coast in the Kaoko Belt. Strong variations in crustal thickness and Vp/Vs ratios are found at the landfall of the Walvis Ridge. Here and at ~150 km northeast of the coast, the crustal thickness increases dramatically reaching 44 km and the Vp/Vs ratios are extremely high (~1.89). These anomalies are interpreted as magmatic underplating produced by the mantle plume during the breakup of Gondwana. The area affected by the plume is smaller than 300 km in diameter, possibly ruling out the existence of a large plume head under the continent during the breakup.

Description: Northwestern Namibia, at the landfall of the Walvis Ridge, was affected by the Tristan da Cunha mantle plume during continental rupture between Africa and South America, as evidenced by the presence of the Etendeka continental flood basalts. Here we use data from a passive-source seismological network to investigate the upper mantle structure and to elucidate the Cretaceous mantle plume-lithosphere interaction. Receiver functions reveal an interface associated with a negative velocity contrast within the lithosphere at an average depth of 80 km. We interpret this interface as the relic of the lithosphereasthenosphere boundary (LAB) formed during the Mesozoic by interaction of the Tristan da Cunha plume head with the pre-existing lithosphere. The velocity contrast might be explained by stagnated and ‘‘frozen’’ melts beneath an intensively depleted and dehydrated peridotitic mantle. The present-day LAB is poorly visible with converted waves, indicating a gradual impedance contrast. Beneath much of the study area, converted phases of the 410 and 660 km mantle transition zone discontinuities arrive 1.5 s earlier than in the landward plume-unaffected continental interior, suggesting high velocities in the upper mantle caused by a thick lithosphere. This indicates that after lithospheric thinning during continental breakup, the lithosphere has increased in thickness during the last 132 Myr. Thermal cooling of the continental lithosphere alone cannot produce the lithospheric thickness required here. We propose that the remnant plume material, which has a higher seismic velocity than the ambient mantle due to melt depletion and dehydration, significantly contributed to the thickening of the mantle lithosphere.

Description: The intermediate-depth seismicity (IDS) beneath the Gibraltar Arc is enigmatic. So far, there is no general consensus on its relationship with the ongoing tectonic processes. We analyzed S wave receiver functions (SRFs) with data recorded by a dense N-S seismic profile deployed across the Sierra Nevada in southern Spain. SRF piercing points at depths of the lithosphere-asthenosphere boundary (LAB) sample an area of the IDS zone, providing an ideal opportunity to study the lithospheric structure at the IDS zone. We observe an abrupt change in the LAB depth along a profile from north to south across the northern branch of the IDS. The LAB depth changes from 90 to 100 km north of the IDS to ~130 km south of it. We propose that the IDS marks a tear in the Iberian mantle lithosphere along its entire length, implying an ongoing lithospheric delamination process that produces the seismicity at its onset.