Expression of haptoglobin in human keratinocytes and Langerhans cells

Wang, H; Xh, Gao; Yk, Wang; P, Li; Cd, He; Xie, Yun; Hd, Chen

doi:10.1111/j.1365-2133.2005.06807.x

Cited by 18 publications

(12 citation statements)

References 27 publications

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“…In this frame, the finding that quantitatively rather than qualitatively changes increase in glycans of skin Hpt, as compared with those of pHpt-P, led us to argue that glycoforms of the former protein population might diffuse from epidermis to blood thus modifying the glycoform composition of circulating Hpt. Hpt with altered glycosylation pattern might be produced by keratinocytes [13] in the skin at the site of inflammation and secreted into the plasma. Our hypothesis on changes and source of psoriasis-associated Hpt glycoforms was strengthened by results from experiments with lectins.…”

Section: Discussionmentioning

confidence: 99%

“…Although the tissue-specific expression of Hpt in some peripheral organs was demonstrated [8]–[12], the role of Hpt in the skin or skin diseases like psoriasis has not yet been studied. Limited studies provide evidence that Hpt might be synthesized and/or secreted into the skin [13], and demonstrate its inhibitory effect on the differentiation of immature epidermal Langerhans cells in antigen presenting cells [14]. Locally produced Hpt might have a modulatory role on skin cells and/or on cells of the immune system, recruited at the site of inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Differences between the Glycosylation Patterns of Haptoglobin Isolated from Skin Scales and Plasma of Psoriatic Patients

et al. 2012

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Improved diagnosis of psoriasis, by new biomarkers, is required for evaluating the progression rate of the disease and the response to treatment. Haptoglobin (Hpt), a glycoprotein secreted by hepatocytes and other types of cells including keratinocytes, was found with glycan changes in psoriasis and other diseases. We previously reported that Hpt isolated from plasma of psoriatic patients is more fucosylated than Hpt of healthy subjects. The aim of this study was to compare the glycosylation pattern of Hpt isolated from skin scales or plasma of patients with psoriasis with that of Hpt from cornified epidermal layer or plasma of healthy subjects. High performance liquid chromatography analysis of the glycans isolated from the protein backbone revealed that glycan patterns from skin and plasma of patients were similar, and mostly displayed quantitative rather than qualitative differences from normal pattern. Biotin-labeled lectins were used to evaluate quantitative differences in the glycoforms of Hpt from plasma and psoriatic skin scales. Hpt from skin and plasma of patients showed more fucosylated and branched glycans than Hpt from plasma of healthy subjects. Tryptic glycopeptides of Hpt were also analyzed by mass spectrometry, and a decreased amount of sialylated glycan chains was found in glycopeptides of skin Hpt, as compared with Hpt from plasma. High levels of glycans with fucosylated and tetra-antennary chains were detected on the peptide NLFLNHSENATAK from Hpt of psoriatic patients. Our data demonstrate that specific changes in glycan structures of Hpt, such as enhanced glycan branching and fucose content, are associated with psoriasis, and that differences between circulating and skin Hpt do exist. A lower extent of glycan fucosylation and branching was found in Hpt from plasma of patients in disease remission. Altered glycoforms might reflect changes of Hpt function in the skin, and could be used as markers of the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differences between the Glycosylation Patterns of Haptoglobin Isolated from Skin Scales and Plasma of Psoriatic Patients

et al. 2012

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“…Hpt is produced in human salivary gland, muscle , lung , and skin . Its arterial synthesis is enhanced after balloon dilatation, and it belongs to a unique set of glycoforms different from the product of the liver .…”

Section: Expression Of Apps In Extrahepatic Tissuesmentioning

confidence: 99%

Acute phase proteins as promising biomarkers: Perspectives and limitations for human and veterinary medicine

Schrödl

Büchler

Wendler

et al. 2016

Proteomics Clinical Apps

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Acute phase proteins (APPs) are highly conserved plasma proteins that are increasingly secreted by the liver in response to a variety of injuries, independently of their location and cause. APPs favor the systemic regulation of defense, coagulation, proteolysis, and tissue repair. Various APPs have been applied as general diagnostic parameters for a long time. Through proteomic techniques, more and more APPs have been discovered to be differentially altered. Since they are not consistently explainable by a stereotypic hepatic expression of sets of APPs, most of these results have unfortunately been neglected or attributed to the nonspecificity of the acute phase reaction. Moreover, it appears that various extrahepatic tissues are also able to express APPs. These extrahepatic APPs show focally specific roles in tissue homeostasis and repair and are released primarily into interstitial and distal fluids. Since these focal proteins might leak into the circulatory system, mixtures of hepatic and extrahepatic APP species can be expected in blood. Hence, a selective alteration of parts of APPs might be expected. There are several hints on multiple molecular forms and fragments of tissue-derived APPs. These differences offer the chance for multiple selective determinations. Thus, specific proteoforms might indeed serve as tissue-specific disease indicators.

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“…Specifically, skin from WT or hp -/-mice was transplanted from male donors, which are HY antigen positive, onto WT female recipients, which are HY antigen negative. Haptoglobin is synthesized within the skin (10)(11)(12), and before transplantation, we determined that lysates from WT (including nonlymphoid and lymphoid subpopulations), but not hp -/-, male skin contained haptoglobin (Supplemental Figure 4, A and B). We also found that hp -/-skin contained CD11c + DCs that were…”

Section: Figurementioning

confidence: 99%

Haptoglobin activates innate immunity to enhance acute transplant rejection in mice

Shen¹,

Song²,

Colangelo³

et al. 2012

J. Clin. Invest.

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Immune tolerance to transplanted organs is impaired when the innate immune system is activated in response to the tissue necrosis that occurs during harvesting and implantation procedures. A key molecule in this immune pathway is the intracellular TLR signal adaptor known as myeloid differentiation primary response gene 88 (MyD88). After transplantation, MyD88 induces DC maturation as well as the production of inflammatory mediators, such as IL-6 and TNF-α. However, upstream activators of MyD88 function in response to transplantation have not been identified. Here, we show that haptoglobin, an acute phase protein, is an initiator of this MyD88-dependent inflammatory process in a mouse model of skin transplantation. Necrotic lysates from transplanted skin elicited higher inflammatory responses in DCs than did nontransplanted lysates, suggesting DC-mediated responses are triggered by factors released during transplantation. Analysis of transplanted lysates identified haptoglobin as one of the proteins upregulated during transplantation. Expression of donor haptoglobin enhanced the onset of acute skin transplant rejection, whereas haptoglobin-deficient skin grafts showed delayed acute rejection and antidonor T cell priming in a MyD88-dependent graft rejection model. Thus, our results show that haptoglobin release following skin necrosis contributes to accelerated transplant rejection, with potential implications for the development of localized immunosuppressive therapies.

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Expression of haptoglobin in human keratinocytes and Langerhans cells

Cited by 18 publications

References 27 publications

Differences between the Glycosylation Patterns of Haptoglobin Isolated from Skin Scales and Plasma of Psoriatic Patients

Differences between the Glycosylation Patterns of Haptoglobin Isolated from Skin Scales and Plasma of Psoriatic Patients

Acute phase proteins as promising biomarkers: Perspectives and limitations for human and veterinary medicine

Haptoglobin activates innate immunity to enhance acute transplant rejection in mice

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