Leigh Marsh

The Discovery of New Deep-Sea Hydrothermal Vent Communities in the Southern Ocean and Implications for Biogeography

A survey of Antarctic waters along the East Scotia Ridge in the Southern Ocean reveals a new vent biogeographic province among previously uncharacterized deep-sea hydrothermal vent communities.

Surface expression of CD74 by type II alveolar epithelial cells: a potential mechanism for macrophage migration inhibitory factor-induced epithelial repair

Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine involved in acute lung injury and other processes such as wound repair and tumor growth. MIF exerts pro-proliferative effects on a variety of cell types including monocytes/macrophages, B cells, and gastric epithelial cell lines through binding to the major histocompatibility complex type II-associated invariant chain, CD74. In acute lung injury, inflammatory damage of the alveolar epithelium leads to loss of type I alveolar epithelial cells (AEC-I), which are replaced by proliferation and differentiation of type II alveolar epithelial cells (AEC-II). In this study we have investigated the potential of MIF to contribute to alveolar repair by stimulating alveolar epithelial cell proliferation. We show that murine AEC-II, but not AEC-I, express high surface levels of CD74 in vivo. Culture of AEC-II in vitro resulted in decreased mRNA levels for CD74 and loss of surface CD74 expression, which correlated with a transition of AEC-II to an AEC-I-like phenotype. MIF stimulation of AEC-II induced rapid and prolonged phosphorylation of ERK1/2 and Akt, increased expression of cyclins D1 and E, as well as AEC-II proliferation. Corresponding MIF signaling and enhanced thymidine incorporation was observed after MIF stimulation of MLE-12 cells transfected to overexpress CD74. In contrast, MIF did not induce MAPK activation, gene transcription, or increased proliferation in differentiated AEC-I-like cells that lack CD74. These data suggest a previously unidentified role of MIF-CD74 interaction by inducing proliferation of AEC-II, which may contribute to alveolar repair.

Macrophage Tumor Necrosis Factor-α Induces Epithelial Expression of Granulocyte–Macrophage Colony-stimulating Factor

RATIONALE Resident alveolar macrophages have been attributed a crucial role in host defense toward pulmonary infection. Their contribution to alveolar repair processes, however, remains elusive. OBJECTIVES We investigated whether activated resident alveolar macrophages contribute to alveolar epithelial repair on lipopolysaccharide (LPS) challenge in vitro and in vivo and analyzed the molecular interaction pathways involved. METHODS We evaluated macrophage-epithelial cross-talk mediators for epithelial cell proliferation in an in vitro coculture system and an in vivo model of LPS-induced acute lung injury comparing wild-type, granulocyte-macrophage colony-stimulating factor (GM-CSF)-deficient (GM(-/-)), and human SPC-GM mice (GM(-/-) mice expressing an SPC-promotor-regulated GM-CSF transgene). MEASUREMENTS AND MAIN RESULTS Using reverse transcription-polymerase chain reaction and ELISA we showed that LPS-activated alveolar macrophages stimulated alveolar epithelial cells (AEC) to express growth factors, particularly GM-CSF, in coculture. Antibody neutralization experiments revealed epithelial GM-CSF expression to be macrophage tumor necrosis factor (TNF)-alpha dependent. GM-CSF elicited proliferative signaling in AEC via autocrine stimulation. Notably, macrophage TNF-alpha induced epithelial proliferation in wild-type but not in GM-CSF-deficient AEC as shown by [(3)H]-thymidine incorporation and cell counting. Moreover, intraalveolar TNF-alpha neutralization impaired AEC proliferation in LPS-injured mice, as investigated by flow cytometric Ki-67 staining. Additionally, GM-CSF-deficient mice displayed reduced AEC proliferation and sustained alveolar barrier dysfunction on LPS treatment compared with wild-type mice. CONCLUSIONS Collectively, these findings indicate that TNF-alpha released from activated resident alveolar macrophages induces epithelial GM-CSF expression, which in turn initiates AEC proliferation and contributes to restoring alveolar barrier function.

Microdistribution of faunal assemblages at deep-sea hydrothermal vents in the Southern Ocean

Chemosynthetic primary production by microbes supports abundant faunal assemblages at deep-sea hydrothermal vents, with zonation of invertebrate species typically occurring along physico-chemical gradients. Recently discovered vent fields on the East Scotia Ridge (ESR) in the Southern Ocean represent a new province of vent biogeography, but the spatial dynamics of their distinct fauna have yet to be elucidated. This study determines patterns of faunal zonation, species associations, and relationships between faunal microdistribution and hydrothermal activity in a vent field at a depth of 2,400 m on the ESR. Remotely operated vehicle (ROV) dives obtained high-definition imagery of three chimney structures with varying levels of hydrothermal activity, and a mosaic image of >250 m2 of seafloor co-registered with temperature measurements. Analysis of faunal microdistribution within the mosaiced seafloor reveals a consistent pattern of faunal zonation with increasing distance from vent sources and peak temperatures. Assemblages closest to vent sources are visibly dominated by a new species of anomuran crab, Kiwa n. sp. (abundance >700 individuals m−2), followed by a peltospiroid gastropod (>1,500 individuals m−2), eolepadid barnacle (>1,500 individuals m−2), and carnivorous actinostolid anemone (>30 individuals m−2). Peripheral fauna are not dominated by a single taxon, but include predatory and scavenger taxa such as stichasterid seastars, pycnogonids and octopus. Variation in faunal microdistribution on chimneys with differing levels of activity suggests a possible successional sequence for vent fauna in this new biogeographic province. An increase in δ34S values of primary consumers with distance from vent sources, and variation in their δ13C values also indicate possible zonation of nutritional modes of the vent fauna. By using ROV videography to obtain a high-resolution representation of a vent environment over a greater extent than previous studies, these results provide a baseline for determining temporal change and investigations of processes structuring faunal assemblages at Southern Ocean vents.

Perspective: Ambient Air Pollution: Inflammatory Response and Effects on the Lung's Vasculature

Particulates from air pollution are implicated in causing or exacerbating respiratory and systemic cardiovascular diseases and are thought to be among the leading causes of morbidity and mortality. However, the contribution of ambient particulate matter to diseases affecting the pulmonary circulation, the right heart, and especially pulmonary hypertension is much less documented. Our own work and that of other groups has demonstrated that prolonged exposure to antigens via the airways can cause severe pulmonary arterial remodeling. In addition, vascular changes have been well documented in a typical disease of the airways, asthma. These experimental and clinical findings link responses in the airways with responses in the lungs vasculature. It follows that particulate air pollution could cause, or exacerbate, diseases in the pulmonary circulation and associated pulmonary hypertension. This perspective details the literature for support of this concept. Data regarding the health effects of particulate matter from air pollution on the lungs vasculature, with emphasis on the lungs inflammatory responses to particulate matter deposition and pulmonary hypertension, are discussed. A deeper understanding of the health implications of exposure to ambient particulate matter will improve our knowledge of how to improve the management of lung diseases, including diseases of the pulmonary circulation. As man-made ambient particulate air pollution is typically linked to economic growth, a better understanding of the health effects of exposure to particulate air pollution is expected to integrate the global goal of achieving healthy living for all.

High-mobility group box-1 induces vascular remodelling processes via c-Jun activation

Extracellular high‐mobility group box‐1 (HMGB1) acts as a signalling molecule during inflammation, cell differentiation and angiogenesis. Increased abundance of HMGB1 is associated with several pathological disorders such as cancer, asthma and chronic obstructive pulmonary disease (COPD). In this study, we investigated the relevance of HMGB1 in the pathological remodelling present in patients with idiopathic pulmonary arterial hypertension (IPAH) and pulmonary hypertension (PH) associated with COPD. Remodelled vessels present in COPD with PH and IPAH lung samples were often surrounded by HMGB1‐positive cells. Increased HMGB1 serum levels were detected in both patient populations compared to control samples. The effects of physiological HMGB1 concentrations were then examined on cellular responses in vitro. HMGB1 enhanced proliferation of pulmonary arterial smooth muscle cells (PASMC) and primary human arterial endothelial cells (PAEC). HMGB1 stimulated p38, extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) phosphorylation. Furthermore, activation of the downstream AP‐1 complex proteins c‐Fos and c‐Jun was observed. Silencing of c‐Jun ablated the HMGB1‐induced proliferation in PASMC. Thus, an inflammatory component such as HMGB1 can contribute to PASMC and PAEC proliferation and therefore potentially to vascular remodelling and PH pathogenesis.

Adaptations to Hydrothermal Vent Life in Kiwa tyleri, a New Species of Yeti Crab from the East Scotia Ridge, Antarctica

Hydrothermal vents in the Southern Ocean are the physiologically most isolated chemosynthetic environments known. Here, we describe Kiwa tyleri sp. nov., the first species of yeti crab known from the Southern Ocean. Kiwa tyleri belongs to the family Kiwaidae and is the visually dominant macrofauna of two known vent sites situated on the northern and southern segments of the East Scotia Ridge (ESR). The species is known to depend on primary productivity by chemosynthetic bacteria and resides at the warm-eurythermal vent environment for most of its life; its short-range distribution away from vents (few metres) is physiologically constrained by the stable, cold waters of the surrounding Southern Ocean. Kiwa tylerihas been shown to present differential life history adaptations in response to this contrasting thermal environment. Morphological adaptations specific to life in warm-eurythermal waters, as found on – or in close proximity of – vent chimneys, are discussed in comparison with adaptations seen in the other two known members of the family (K. hirsuta, K. puravida), which show a preference for low temperature chemosynthetic environments.

Interleukin 13– and interleukin 17A–induced pulmonary hypertension phenotype due to inhalation of antigen and fine particles from air pollution

Pulmonary hypertension has a marked detrimental effect on quality of life and life expectancy. In a mouse model of antigen-induced pulmonary arterial remodeling, we have recently shown that coexposure to urban ambient particulate matter (PM) significantly increased the thickening of the pulmonary arteries and also resulted in significantly increased right ventricular systolic pressures. Here we interrogate the mechanism and show that combined neutralization of interleukin 13 (IL-13) and IL-17A significantly ameliorated the increase in right ventricular systolic pressure, the circumferential muscularization of pulmonary arteries, and the molecular change in the right ventricle. Surprisingly, our data revealed a protective role of IL-17A for the antigen- and PM-induced severe thickening of pulmonary arteries. This protection was due to the inhibition of the effects of IL-13, which drove this response, and the expression of metalloelastase and resistin-like molecule α. However, the latter was redundant for the arterial thickening response. Anti-IL-13 exacerbated airway neutrophilia, which was due to a resulting excess effect of IL-17A, confirming concurrent cross inhibition of IL-13- and IL-17A-dependent responses in the lungs of animals exposed to antigen and PM. Our experiments also identified IL-13/IL-17A-independent molecular reprogramming in the lungs induced by exposure to antigen and PM, which indicates a risk for arterial remodeling and protection from arterial constriction. Our study points to IL-13- and IL-17A-coinduced inflammation as a new template for biomarkers and therapeutic targeting for the management of immune response–induced pulmonary hypertension.

Geochemical and Visual Indicators of Hydrothermal Fluid Flow through a Sediment-Hosted Volcanic Ridge in the Central Bransfield Basin (Antarctica)

In the austral summer of 2011 we undertook an investigation of three volcanic highs in the Central Bransfield Basin, Antarctica, in search of hydrothermal activity and associated fauna to assess changes since previous surveys and to evaluate the extent of hydrothermalism in this basin. At Hook Ridge, a submarine volcanic edifice at the eastern end of the basin, anomalies in water column redox potential (Eh) were detected close to the seafloor, unaccompanied by temperature or turbidity anomalies, indicating low-temperature hydrothermal discharge. Seepage was manifested as shimmering water emanating from the sediment and from mineralised structures on the seafloor; recognisable vent endemic fauna were not observed. Pore fluids extracted from Hook Ridge sediment were depleted in chloride, sulfate and magnesium by up to 8% relative to seawater, enriched in lithium, boron and calcium, and had a distinct strontium isotope composition (87Sr/86Sr  = 0.708776 at core base) compared with modern seawater (87Sr/86Sr ≈0.70918), indicating advection of hydrothermal fluid through sediment at this site. Biogeochemical zonation of redox active species implies significant moderation of the hydrothermal fluid with in situ diagenetic processes. At Middle Sister, the central ridge of the Three Sisters complex located about 100 km southwest of Hook Ridge, small water column Eh anomalies were detected but visual observations of the seafloor and pore fluid profiles provided no evidence of active hydrothermal circulation. At The Axe, located about 50 km southwest of Three Sisters, no water column anomalies in Eh, temperature or turbidity were detected. These observations demonstrate that the temperature anomalies observed in previous surveys are episodic features, and suggest that hydrothermal circulation in the Bransfield Strait is ephemeral in nature and therefore may not support vent biota.

Paxillin Regulates Pulmonary Arterial Smooth Muscle Cell Function in Pulmonary Hypertension

Pulmonary hypertension (PH) is a fatal disease characterized by remodeling processes such as increased migration and proliferation of pulmonary arterial smooth muscle cells (PASMC), enhanced matrix deposition, and dysregulation of cytoskeletal proteins. However, the contribution of cytoskeletal proteins in PH is still not fully understood. In this study, we have used a yeast two-hybrid screen to identify novel binding partners of the cytoskeletal adaptor protein four-and-a-half LIM domains 1 (Fhl-1). This identified paxillin as a new Fhl-1 interacting partner, and consequently we assessed its contribution to vascular remodeling processes. Native protein-protein binding was confirmed by co-immunoprecipitation studies in murine and human PASMC. Both proteins co-localized in PASMC in vitro and in vivo. In lung samples from idiopathic pulmonary arterial hypertension patients, paxillin expression was increased on mRNA and protein levels. Laser-microdissection of murine intrapulmonary arteries revealed elevated paxillin expression in hypoxia-induced PH. Furthermore, hypoxia-dependent upregulation of paxillin was HIF-1α dependent. Silencing of paxillin expression led to decreased PASMC adhesion, proliferation, and increased apoptosis. Regulation of these processes occurred via Akt and Erk1/2 kinases. In addition, adhesion of PASMC to the extracellular matrix protein fibronectin was critically dependent on paxillin expression. To summarize, we identified paxillin as a new regulator protein of PASMC growth.