The novel acute phase protein, IHRP, inhibits actin polymerization and phagocytosis of polymorphonuclear cells

Choi-Miura, Nam-Ho; Takahashi, K.; Yoda, Madoka; Saito, Kiyomi; Hori, Masaru; Ozaki, Hiroshi; Mazda, Toshio; Tomita, Mizuki

doi:10.1007/pl00000211

Cited by 40 publications

(32 citation statements)

References 32 publications

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“…The consistently low levels of haptoglobin (and precursor) as well as of hyaluronidase and IHRP in Hampshire pigs confirm the absence of inflammatory processes. Hence, hyaluronidase limits the permeability of the respiratory barrier, and IHRP is considered to reduce the phagocytic activity of PMN by inhibiting the polymerization of cell surface actin [8].…”

Section: Discussionmentioning

confidence: 99%

Glycoprotein analysis of porcine bronchoalveolar lavage fluid reveals potential biomarkers corresponding to resistance toActinobacillus pleuropneumoniaeinfection

D¹,

Buettner²,

Naim³

et al. 2009

Vet. Res.

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-Biomarkers facilitating both pathogen-independent diagnosis of respiratory health and breeding selection of pigs with increased resistance to respiratory tract infections would be of considerable interest to the pig industry. Following this concept we performed a comparative glycoproteome analysis of bronchoalveolar lavage fluid (BALF) from healthy pigs and pigs 4 days (acute) and 20 days (chronic) after an experimental infection with Actinobacillus pleuropneumoniae. In order to identify possible differences in BALF glycoprotein patterns we investigated pigs of three different breeding lines (German Landrace, Piétrain, Hampshire). In total, 12 glycosylated proteins (alpha-1-acid glycoprotein, fetuin A, properdin, haptoglobin precursor, haptoglobin, hemoglobin, hyaluronidase, inter-alpha-trypsin inhibitor family heavy chain-related protein, alpha-1-antichymotrypsin 3, pulmonary surfactant-associated protein D (SP-D), transferrin, and alpha-1B-glycoprotein) were identified as being differentially expressed depending on the health status of the animal. Fetuin A levels were consistently low in chronically infected pigs thereby being a potential marker for chronic infection. Hyaluronidase levels were consistently high in all pigs after experimental infection independent on isolation of the pathogen thereby being a potential marker for previous pathogen contact and latent infection. High levels of fetuin A as well as low levels of haptoglobin and pulmonary SP-D correlated with the absence of lung lesions in pigs of the Hampshire breeding line, implying a potential application as selection markers for breeding programmes.porcine respiratory disease / glycoprotein analysis / bronchoalveolar lavage fluid / biomarker

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Section: Discussionmentioning

confidence: 99%

Glycoprotein analysis of porcine bronchoalveolar lavage fluid reveals potential biomarkers corresponding to resistance toActinobacillus pleuropneumoniaeinfection

D¹,

Buettner²,

Naim³

et al. 2009

Vet. Res.

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“…Pig-MAP/ITH4 has been shown to be expressed in the endometrium during the oestrous cycle and early pregnancy in pigs [14]. Recent studies suggest that the ITIH4 may act as an anti-inflammatory protein since it has been shown that this protein can inhibit actin polymerisation and phagocytosis of polymorphonuclear cells [9].…”

Section: Discussionmentioning

confidence: 99%

Haptoglobin and pig-major acute protein are increased in pigs with postweaning multisystemic wasting syndrome (PMWS)

Segalés

Piñeiro²,

Lampreave

et al. 2004

Vet. Res.

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-The objective of this study was to determine the serum concentration levels of selected acute phase proteins (APP), haptoglobin (HPT) and pig-major acute phase protein (pig-MAP), in postweaning multisystemic wasting syndrome (PMWS) affected pigs and PCV2-subclinically infected pigs. In a first study, a group of 15 eight-week-old conventional pigs from a PMWS affected farm were bled and a complete necropsy, histopathology and in situ hybridisation to detect PCV2 were performed. Based on the results, pigs were classified as suffering from PMWS (n = 10) or healthy animals (n = 5). In a second study, a group of 45 pigs from another PMWS affected farm were selected and bled at 3, 7, 12 and 28 weeks of age. The assessment of PCV2 infection status in these pigs was retrospectively done by PCV2 PCR in serum samples. Selected APP were measured in the serum of all studied pigs by means of radial immunodiffusion. Mean HPT and pig-MAP levels were significantly increased (p = 0.004 and p = 0.0006 respectively) in PMWS-affected pigs when compared to levels found in healthy pigs (2.52 ± 0.88 mg/mL vs. 1.06 ± 0.73 mg/mL for HPT and 3.81 ± 1.53 mg/mL vs. 0.76 ± 0.34 mg/mL for pig-MAP). In the second study, no significant difference in mean HPT and pig-MAP values were observed between PCV2 PCR positive and negative pigs of any age. However, both APP increased significantly with age in PCV2 PCR negative pigs. Altogether, the present results suggest that APP levels are significantly increased in pigs that develop PMWS, but not in animals with a PCV2 subclinical infection. porcine circovirus type 2 (PCV2) / postweaning multisystemic wasting syndrome (PMWS) / acute phase proteins / haptoglobin / pig major acute phase protein (pig-MAP)

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“…It does not have the conserved cleavage site of HC1-3 that allows them to link with bikunin. It does, however, bind to and block the polymerization of actin, resulting in inhibition of neutrophil phagocytosis and chemotaxis (21). The more recently described HC5 has not yet been fully characterized; nor has it been shown to complex with chondroitin sulfate to form I␣I (or pre-I␣I).…”

mentioning

confidence: 99%

Tumor Necrosis Factor-stimulated Gene 6 (TSG-6)-mediated Interactions with the Inter-α-inhibitor Heavy Chain 5 Facilitate Tumor Growth Factor β1 (TGFβ1)-dependent Fibroblast to Myofibroblast Differentiation

Martin

Midgley

Meran

et al. 2016

Journal of Biological Chemistry

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Fibroblasts are central to wound healing and fibrosis through TGF␤1-triggered differentiation into contractile, ␣-smooth muscle actin (␣-SMA)-positive myofibroblasts. This is mediated by accumulation of a pericellular matrix of hyaluronan (HA) and the HA-dependent co-localization of CD44 with the epidermal growth factor receptor (EGFR). Interactions of HA with hyaladherins, such as inter-␣-inhibitor (I␣I) and tumor necrosis factor-stimulated gene-6 (TSG-6), are also essential for differentiation. This study investigated the mechanisms involved. TSG-6 and ␣-SMA had different kinetics of induction by TGF␤1, with TSG-6 peaking before ␣-SMA. Si CD44 or EGFR inhibition prevented differentiation but had no effect on TSG-6 expression. TSG-6 was essential for differentiation, and mAb A38 (preventing I␣I heavy chain (HC) transfer), HA-oligosaccharides, cobalt, or Si bikunin prevented TSG-6 activity, preventing differentiation. A38 also prevented the EGFR/CD44 association. This suggested that TSG-6/I␣I HC interaction was necessary for the effect of TSG-6 and that HC stabilization of HA initiated the CD44/EGFR association. The newly described HC5 was shown to be the principal HC expressed, and its cell surface expression was prevented by siRNA inhibition of TSG-6 or bikunin. HC5 was released by hyaluronidase treatment, confirming its association with cell surface HA. Finally, HC5 knockdown by siRNA confirmed its role in myofibroblast differentiation. The current study describes a novel mechanism linking the TSG-6 transfer of the newly described HC5 to the HA-dependent control of cell phenotype. The interaction of HC5 with cell surface HA was essential for TGF␤1-dependent differentiation of fibroblasts to myofibroblasts, highlighting its importance as a novel potential therapeutic target.The fibroblast is the most abundant cell type in normal connective tissues. It plays a central role in the synthesis, degradation, and remodeling of extracellular matrix both in health and in disease. At sites of tissue damage and in the context of wound healing, activated fibroblasts, termed myofibroblasts, with a contractile phenotype, characterized by the expression of the smooth muscle isoform of ␣-actin (␣-SMA), 3 are essential for the synthesis of a collagen-rich scar, providing the force for wound contraction (1). During a healing response, myofibroblasts are a transient cell population (2). Myofibroblasts are also the major effectors of fibrosis; their persistent presence has been established as the best marker of numerous types of progressive organ dysfunction, such as that seen in chronic renal failure of various etiologies (3-7), liver disease (8), and pulmonary fibrosis (9).The cytokine TGF␤1 is a well recognized mediator of progressive tissue fibrosis, and in vitro and in vivo evidence suggests that it is the primary driving force in fibroblast-myofibroblast phenotypic activation (10, 11). The sequence of events leading up to this transformation is being increasingly characterized at a molecular level in an attempt to understan...

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The novel acute phase protein, IHRP, inhibits actin polymerization and phagocytosis of polymorphonuclear cells

Cited by 40 publications

References 32 publications

Glycoprotein analysis of porcine bronchoalveolar lavage fluid reveals potential biomarkers corresponding to resistance toActinobacillus pleuropneumoniaeinfection

Glycoprotein analysis of porcine bronchoalveolar lavage fluid reveals potential biomarkers corresponding to resistance toActinobacillus pleuropneumoniaeinfection

Haptoglobin and pig-major acute protein are increased in pigs with postweaning multisystemic wasting syndrome (PMWS)

Tumor Necrosis Factor-stimulated Gene 6 (TSG-6)-mediated Interactions with the Inter-α-inhibitor Heavy Chain 5 Facilitate Tumor Growth Factor β1 (TGFβ1)-dependent Fibroblast to Myofibroblast Differentiation

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