Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing

Ashcroft, Gillian S.; Lei, Ke-Jian; Jin, Wenwen; Longenecker, Glenn; Kulkarni, Ashok B.; Greenwell-Wild, Teresa; Hale-Donze, Hollie; McGrady, George; Song, Xiao Yu; Wahl, Sharon M.

doi:10.1038/80489

Cited by 377 publications

(357 citation statements)

References 42 publications

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“…Measurement of these parameters are not only essential to monitor the absence of local inflammation in bone chamber implants but also necessary to understand the complex interactions of the microenvironment in bone tissue. Several observations confirm that leukocytes play an important role in fracture repair and wound healing and a disturbance of leukocyte homeostasis in tissue leads to impairment of tissue regeneration [5,6,26,41,44]. Here we present for the first time the time-dependent alterations in interactions between leukocytes and endothelium of bone vessels quantitatively, following a surgical procedure to bone.…”

Section: Discussionsupporting

confidence: 60%

Femur window—a new approach to microcirculation of living bone in situ

Hansen-Algenstaedt

Schaefer

Wolfram

et al. 2005

Journal Orthopaedic Research

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Background: The processes of osteogenesis, bone remodelling, fracture repair and metastasis to bone are determined by complex sequential interactions involving cellular and microcirculatory parameters. Consequently studies targeting the analysis of microcirculatory parameters on such processes should mostly respect these complex conditions. However these conditions could not yet be achieved in vitro and therefore techniques that allow a long-term observation of functional and structural parameters of microcirculation in bone in vivo at a high spatial resolution are needed to monitor dynamic events, such as fracture healing, bone remodelling and tumor metastasis.Methods: We developed a bone chamber implant (femur window) for long-term intravital microscopy of pre-existing bone and its microcirculation at an orthotopic site in mice preserving the mechanical properties of bone. After bone chamber implantation vascular density, vessel diameter, vessel perfusion, vascular permeability and leukocyte-endothelial interactions (LEIS) in femoral bone tissue of c57-black mice ( n = 11) were measured quantitatively over 12 days using intravital fluorescence microscopy. Furthermore a model for bone defect healing and bone metastasis in the femur window was tested.Results: Microvascular permeability and LEIS showed initially high values after chamber implantation followed by a significant decrease to a steady state at day 6 and 12, whereas structural parameters remained unaltered. Bone defect healing and tumor growth was observed over 12 and 90 days respectively. Conclusion:The new femur window design allows a long-term analysis of structural and functional properties of bone and its microcirculation quantitatively at a high spatial resolution. Altered functional parameters of microcirculation after surgical procedures and their time dependent return to a steady state underline the necessity of long-term observations to achieve unaltered microcirculatory parameters. Dissection of the complex interactions between bone and microcirculation enables us to evaluate physiological and pathological processes of bone and may give new insights especially in dynamic events e.g. fracture healing, bone remodeling and tumor metastasis.

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Section: Discussionsupporting

confidence: 60%

Femur window—a new approach to microcirculation of living bone in situ

Hansen-Algenstaedt

Schaefer

Wolfram

et al. 2005

Journal Orthopaedic Research

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“…Recently Ashcroft et al (52) reported that SLPI-null mice had impaired cutaneous wound healing with increased inflammation. Our results imply that SLPI plays a role in controlling the inflammatory response in the acute cutaneous wound during phagocytosis of apoptotic cells, and may help to explain why wound healing is impaired in SLPI-null mice (52).…”

Section: Discussionmentioning

confidence: 99%

Murine Macrophages Produce Secretory Leukocyte Protease Inhibitor During Clearance of Apoptotic Cells: Implications for Resolution of the Inflammatory Response

Odaka

Mizuochi

Yang

et al. 2003

The Journal of Immunology

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Macrophage-derived secretory leukocyte protease inhibitor (SLPI) can be induced locally as well as systemically in response to microbial products such as LPS and lipotechoic acid. It is not known whether phagocytosis of apoptotic cells, an essential function of macrophages, can regulate expression and secretion of SLPI. In this study, we report that exposure of peritoneal macrophages of BALB/c mice or murine macrophage cell lines RAW264.7 and J774.1 to apoptotic target cells induced an elevation in SLPI secretion. Secreted SLPI retained its antichymotrypsin activity. SLPI expression in thymuses from BALB/c mice that had been injected with anti-CD3 Ab to induce apoptosis of thymocytes was also elevated both at the mRNA and protein levels. Colchicine, a microtubular inhibitor, blocked the internalization of apoptotic cells by macrophages but not SLPI secretion, suggesting that surface recognition of apoptotic cells is sufficient for the induction of SLPI. Exposure of RAW264.7 cells to apoptotic CTLL-2 cells induced both SLPI and TNF-α, and addition of IFN-γ inhibited SLPI but augmented TNF-α production. Transfection of either the secreted or a nonsecreted form of SLPI into RAW264.7 cells led to suppression of TNF-α production in response to apoptotic cells. Thus, macrophages secrete an increased amount of SLPI when encountering apoptotic cells, which may help to attenuate potential inflammation during clearance of these cells.

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“…Our results suggest that Pdp11 may avoid deleterious effects in skin. In addition, it was found that LEI has antimicrobial properties in mucosal fluids [57] and is up-regulated by cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) [58]. Based on this, LEI under-expression in overcrowding stress fish may suggest an increased susceptibility of skin to infections.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Differential proteome profile of skin mucus of gilthead seabream (Sparus aurata) after probiotic intake and/or overcrowding stress

Cordero¹,

Morcillo

Cuesta

et al. 2016

Journal of Proteomics

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Differential proteome profile of skin mucus of gilthead seabream (sparus aurata) after probiotic intake and/or overcrowding stress, Journal of Proteomics (2015Proteomics ( ), doi: 10.1016Proteomics ( /j.jprot.2015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E DM A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 AbstractGilthead seabream (Sparus aurata L.) is the major cultured fish species in the Mediterranean area. High density stocking causes stress and increases the impact of diseases leading to economic losses. Probiotics could represent a solution to prevent diseases through several mechanisms such as improving the immune status and/or mucosal microbiota or competing with pathogens. The probiotic Shewanella putrefaciens, also known as Pdp11, was firstly isolated from the skin of healthy gilthead seabream. Our study focuses on the skin mucus proteome after dietary probiotic Pdp11 intake in fish maintained under normal or overcrowding conditions. 2-DE of skin mucus followed by LC-MS/MS analysis was done for each experimental group and differentially expressed proteins were identified. The results showed differentially expressed proteins especially involved in immune processes, such as lysozyme, complement C3, natural killer cell enhancing factor and nonspecific cytotoxic cell receptor protein 1, whose transcript profiles were studied by qPCR. A consistency between lysozyme protein levels in the mucus and lysozyme mRNA levels in skin were found. Further research is necessary to unravel the implications of skin mucosal immunity on fish welfare and disease. Biological significanceThe present work reveals the proteomic changes, which are taking place in the skin mucus of stressed and non-stressed gilthead seabream after Pdp11 probiotic intake. The study contributes to improve the knowledge on skin mucosal immunology of this relevant farmed fish species.Furthermore, the paper shows for the first time how a suitable proteomic methodology, in this case 2-DE followed by LC-MS/MS is useful to perform a comparative study with a noninvasive technique of skin mucus of gilthead seabream.

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Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing

Cited by 377 publications

References 42 publications

Femur window—a new approach to microcirculation of living bone in situ

Femur window—a new approach to microcirculation of living bone in situ

Murine Macrophages Produce Secretory Leukocyte Protease Inhibitor During Clearance of Apoptotic Cells: Implications for Resolution of the Inflammatory Response

Differential proteome profile of skin mucus of gilthead seabream (Sparus aurata) after probiotic intake and/or overcrowding stress

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