Tamm Horsfall Glycoprotein

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  • Tamm-Horsfall Glycoprotein: biology and clinical relevance
    American journal of kidney diseases : the official journal of the National Kidney Foundation, 2003
    Co-Authors: Franca Serafini-cessi, Nadia Malagolini, Daniela Cavallone
    Abstract:

    Tamm-Horsfall Glycoprotein (THP) is the most abundant urinary protein in mammals. Urinary excretion occurs by proteolytic cleavage of the large ectodomain of the glycosyl phosphatidylinositol-anchored counterpart exposed at the luminal cell surface of the thick ascending limb of Henle's loop. We describe the physical-chemical structure of human THP and its biosynthesis and interaction with other proteins and leukocytes. The clinical relevance of THP reported here includes: (1) involvement in the pathogenesis of cast nephropathy, urolithiasis, and tubulointerstitial nephritis; (2) abnormalities in urinary excretion in renal diseases; and (3) the recent finding that familial juvenile hyperuricemic nephropathy and autosomal dominant medullary cystic kidney disease 2 arise from mutations of the THP gene. We critically examine the literature on the physiological role and mechanism(s) that promote urinary excretion of THP. Some lines of research deal with the in vitro immunoregulatory activity of THP, termed uromodulin when isolated from urine of pregnant women. However, an immunoregulatory function in vivo has not yet been established. In the most recent literature, there is renewed interest in the capacity of urinary THP to compete efficiently with urothelial cell receptors, such as uroplakins, in adhering to type 1 fimbriated Escherichia coli. This property supports the notion that abundant THP excretion in urine is promoted in the host by selective pressure to obtain an efficient defense against urinary tract infections caused by uropathogenic bacteria.

  • Salt-precipitation method does not isolate to homogeneity Tamm-Horsfall Glycoprotein from urine of proteinuric patients and pregnant women
    Clinical biochemistry, 2002
    Co-Authors: Daniela Cavallone, Nadia Malagolini, Giovanni-maria Frascà, Sergio Stefoni, Franca Serafini-cessi
    Abstract:

    Abstract Objective: Assessment of the degree of purification of Tamm-Horsfall Glycoprotein from anomalous urine. Design and methods: Two methods have been compared: the method of Tamm & Horsfall (T&H method) consisting in the precipitation of THP by the addition to urine of NaCl up to 0.58 mol/L and the filtration of urine through a diatomaceous earth filter (DEF method) in which THP is selectively trapped because of its gelation/aggregation tendency. The purity of THP preparations has been evaluated by SDS-PAGE analysis and Western blotting developed with anti immunoglobulin G (IgG) antibodies and antichorionic gonadotropin antibodies. Results: All THPs isolated by T&H method from proteinuric patients were contaminated by IgG and one of the five preparations from pregnant women even by chorionic gonadotropin. A smaller or no contamination was found in THPs isolated by DEF method. Conclusions: Although albumin is the most abundant protein in the anomalous urine, it never appears in THP preparations. The consistent contamination with IgG of THP prepared by salt precipitation-method might be related to the formation of a stable complex between the two proteins.

  • Mechanism of Release of Urinary Tamm-Horsfall Glycoprotein from the Kidney GPI-Anchored Counterpart☆
    Biochemical and biophysical research communications, 2001
    Co-Authors: Daniela Cavallone, Nadia Malagolini, Franca Serafini-cessi
    Abstract:

    Human Tamm-Horsfall Glycoprotein (THP) is synthesised in the thick ascending limb of Henle and convoluted distal tubules, inserted into luminal cell-surface by the glycosyl-phosphatidylinositol (GPI)-anchor and excreted in urine at a rate of 50-100 mg per day. Up to date there is no indication on the way in which THP is excreted into the urinary fluid. In this study, we examined by Western blotting THP from human kidney in comparison to urinary THP. As expected for a GPI-anchored protein, THP was recovered from the kidney lysate in a Triton X-100 insoluble form, which moved in a sucrose gradient to a zone of low density. The apparent molecular weight of kidney THP appeared greater than that of urinary THP, but no difference in the electrophoretic mobility was observed when the former was subjected to GPI-specific phospholipase-C treatment, strongly suggesting that a proteolytic cleavage at the juxtamembrane-ectodomain of kidney THP is responsible for the urinary excretion.

  • Binding of human neutrophils to cell-surface anchored Tamm-Horsfall Glycoprotein in tubulointerstitial nephritis.
    Kidney international, 1999
    Co-Authors: Daniela Cavallone, Nadia Malagolini, Franca Serafini-cessi
    Abstract:

    Binding of human neutrophils to cell-surface anchored Tamm-Horsfall Glycoprotein in tubulointerstitial nephritis. Background Human Tamm-Horsfall Glycoprotein (T-H) is a glycosylphosphatidylinositol-anchored protein exposed at the surface of distal nephron cells, and urinary T-H is the released soluble counterpart. The latter has been implicated in tubulointerstitial nephritis, and the proinflammatory potential has been related to its ability to bind in vitro human neutrophils (PMNs). We have examined the conditions required for the binding of neutrophils to cell-surface anchored T-H and the consequent effects. Methods A HeLa cell-line derivative permanently transformed with human T-H cDNA and expressing T-H at the cell surface was used throughout the study. The adhesion of PMNs to cells expressing T-H was analyzed by immunofluorescence microscopy before and after the opsonization of cells with anti–T-H antibodies. The oxidative burst induced by adhesion of PMNs to the cells was determined by the activation of myeloperoxidase. Quantitative and qualitative changes in the release of T-H under the adhesion of activated PMNs were determined by dot-blot and Western blot analysis. Results No binding of neutrophils to cell-surface–anchored T-H was observed. On the contrary, the opsonization of cells with anti–T-H antibodies resulted in a dramatic adhesion of neutrophils. Such an adhesion induced the oxidative burst of PMNs and a large increment in the release of T-H, as well as the release of the slightly faster migrating T-H form, which is normally retained intracellularly. Conclusions These results support the notion that, after the autoimmune response, the adhesion of neutrophils to cell-surface T-H contributes to the pathogenesis of tubulointerstitial nephritis, favoring a further accumulation of T-H in the interstitium and inducing the loss of cell integrity via reactive oxygen metabolites generated by activated neutrophils.

  • Intracellular transport, cell-surface exposure and release of recombinant Tamm-Horsfall Glycoprotein.
    Kidney international, 1997
    Co-Authors: Nadia Malagolini, Daniela Cavallone, Franca Serafini-cessi
    Abstract:

    Intracellular transport, cell-surface exposure and release of recombinant Tamm-Horsfall Glycoprotein. Human Tamm-Horsfall Glycoprotein (T-H), first described as the major urinary Glycoprotein, is a glycosylphosphatidyl-inositol (GPI)-anchored membrane protein which mainly resides at the luminal face of cells of the thick ascending limb of Henle's loop (TAL) and early distal convoluted tubules of nephron. Since no human renal cell-line producing T-H is available, T-H cDNA was transfected in HeLa cells and a cell line was selected in which 95% of the cells stably expressed T-H, in order to elucidate the biosynthesis, mechanisms regulating the transport of T-H along the exocytic pathway, exposure at the cell surface and release in soluble form. Treatment of cells with an exogenous reducing agent results in a drastic delay in the conversion from precursor to mature T-H. Since the accumulating T-H-precursor carries glycans not yet processed by Golgi-mannosidases, we propose that the formation of a correct set of intrachain disulphide bonds is required for T-H exit out the endoplasmic reticulum. Even the treatment of cells with an inhibitor of GPI-anchor biosynthesis results in an intracellular accumulation of T-H precursor, loss of T-H localization into Golgi apparatus and reduced surface exposure. These results indicate that the GPI-anchor addition is necessary for T-H delivery to the cell-surface. The release rate of new synthesized T-H shows an initial lag time very likely depending on the time required for T-H surface exposure. A portion of released T-H appears to contain ethanolamine, a component of GPI anchor, indicating that, at least in HeLa cells, a GPI-specific phospholipase contributes to the T-H release. Exposure of cells to monensin and brefeldin A results in a loss of accumulation of T-H in the Golgi perinuclear region and a reduced delivery to the cell surface. Under monensin treatment an intermediate T-H form non-exposed at the cell surface is released in the medium, indicating that a soluble T-H may be produced inside the cell under conditions that alter the Golgi apparatus. If such an event occurs in polarized kidney cells, a T-H release from the basolateral face may be postulated, inasmuch as the GPI-anchor is an apical sorting signal. Since T-H is a powerful autoantigen, the accumulation of soluble T-H in the interstitium of TAL may cause the formation of immunocomplexes.

Kathryn A. Patras - One of the best experts on this subject based on the ideXlab platform.

Daniela Cavallone - One of the best experts on this subject based on the ideXlab platform.

  • Tamm-Horsfall Glycoprotein: biology and clinical relevance
    American journal of kidney diseases : the official journal of the National Kidney Foundation, 2003
    Co-Authors: Franca Serafini-cessi, Nadia Malagolini, Daniela Cavallone
    Abstract:

    Tamm-Horsfall Glycoprotein (THP) is the most abundant urinary protein in mammals. Urinary excretion occurs by proteolytic cleavage of the large ectodomain of the glycosyl phosphatidylinositol-anchored counterpart exposed at the luminal cell surface of the thick ascending limb of Henle's loop. We describe the physical-chemical structure of human THP and its biosynthesis and interaction with other proteins and leukocytes. The clinical relevance of THP reported here includes: (1) involvement in the pathogenesis of cast nephropathy, urolithiasis, and tubulointerstitial nephritis; (2) abnormalities in urinary excretion in renal diseases; and (3) the recent finding that familial juvenile hyperuricemic nephropathy and autosomal dominant medullary cystic kidney disease 2 arise from mutations of the THP gene. We critically examine the literature on the physiological role and mechanism(s) that promote urinary excretion of THP. Some lines of research deal with the in vitro immunoregulatory activity of THP, termed uromodulin when isolated from urine of pregnant women. However, an immunoregulatory function in vivo has not yet been established. In the most recent literature, there is renewed interest in the capacity of urinary THP to compete efficiently with urothelial cell receptors, such as uroplakins, in adhering to type 1 fimbriated Escherichia coli. This property supports the notion that abundant THP excretion in urine is promoted in the host by selective pressure to obtain an efficient defense against urinary tract infections caused by uropathogenic bacteria.

  • Salt-precipitation method does not isolate to homogeneity Tamm-Horsfall Glycoprotein from urine of proteinuric patients and pregnant women
    Clinical biochemistry, 2002
    Co-Authors: Daniela Cavallone, Nadia Malagolini, Giovanni-maria Frascà, Sergio Stefoni, Franca Serafini-cessi
    Abstract:

    Abstract Objective: Assessment of the degree of purification of Tamm-Horsfall Glycoprotein from anomalous urine. Design and methods: Two methods have been compared: the method of Tamm & Horsfall (T&H method) consisting in the precipitation of THP by the addition to urine of NaCl up to 0.58 mol/L and the filtration of urine through a diatomaceous earth filter (DEF method) in which THP is selectively trapped because of its gelation/aggregation tendency. The purity of THP preparations has been evaluated by SDS-PAGE analysis and Western blotting developed with anti immunoglobulin G (IgG) antibodies and antichorionic gonadotropin antibodies. Results: All THPs isolated by T&H method from proteinuric patients were contaminated by IgG and one of the five preparations from pregnant women even by chorionic gonadotropin. A smaller or no contamination was found in THPs isolated by DEF method. Conclusions: Although albumin is the most abundant protein in the anomalous urine, it never appears in THP preparations. The consistent contamination with IgG of THP prepared by salt precipitation-method might be related to the formation of a stable complex between the two proteins.

  • Mechanism of Release of Urinary Tamm-Horsfall Glycoprotein from the Kidney GPI-Anchored Counterpart☆
    Biochemical and biophysical research communications, 2001
    Co-Authors: Daniela Cavallone, Nadia Malagolini, Franca Serafini-cessi
    Abstract:

    Human Tamm-Horsfall Glycoprotein (THP) is synthesised in the thick ascending limb of Henle and convoluted distal tubules, inserted into luminal cell-surface by the glycosyl-phosphatidylinositol (GPI)-anchor and excreted in urine at a rate of 50-100 mg per day. Up to date there is no indication on the way in which THP is excreted into the urinary fluid. In this study, we examined by Western blotting THP from human kidney in comparison to urinary THP. As expected for a GPI-anchored protein, THP was recovered from the kidney lysate in a Triton X-100 insoluble form, which moved in a sucrose gradient to a zone of low density. The apparent molecular weight of kidney THP appeared greater than that of urinary THP, but no difference in the electrophoretic mobility was observed when the former was subjected to GPI-specific phospholipase-C treatment, strongly suggesting that a proteolytic cleavage at the juxtamembrane-ectodomain of kidney THP is responsible for the urinary excretion.

  • Binding of human neutrophils to cell-surface anchored Tamm-Horsfall Glycoprotein in tubulointerstitial nephritis.
    Kidney international, 1999
    Co-Authors: Daniela Cavallone, Nadia Malagolini, Franca Serafini-cessi
    Abstract:

    Binding of human neutrophils to cell-surface anchored Tamm-Horsfall Glycoprotein in tubulointerstitial nephritis. Background Human Tamm-Horsfall Glycoprotein (T-H) is a glycosylphosphatidylinositol-anchored protein exposed at the surface of distal nephron cells, and urinary T-H is the released soluble counterpart. The latter has been implicated in tubulointerstitial nephritis, and the proinflammatory potential has been related to its ability to bind in vitro human neutrophils (PMNs). We have examined the conditions required for the binding of neutrophils to cell-surface anchored T-H and the consequent effects. Methods A HeLa cell-line derivative permanently transformed with human T-H cDNA and expressing T-H at the cell surface was used throughout the study. The adhesion of PMNs to cells expressing T-H was analyzed by immunofluorescence microscopy before and after the opsonization of cells with anti–T-H antibodies. The oxidative burst induced by adhesion of PMNs to the cells was determined by the activation of myeloperoxidase. Quantitative and qualitative changes in the release of T-H under the adhesion of activated PMNs were determined by dot-blot and Western blot analysis. Results No binding of neutrophils to cell-surface–anchored T-H was observed. On the contrary, the opsonization of cells with anti–T-H antibodies resulted in a dramatic adhesion of neutrophils. Such an adhesion induced the oxidative burst of PMNs and a large increment in the release of T-H, as well as the release of the slightly faster migrating T-H form, which is normally retained intracellularly. Conclusions These results support the notion that, after the autoimmune response, the adhesion of neutrophils to cell-surface T-H contributes to the pathogenesis of tubulointerstitial nephritis, favoring a further accumulation of T-H in the interstitium and inducing the loss of cell integrity via reactive oxygen metabolites generated by activated neutrophils.

  • Intracellular transport, cell-surface exposure and release of recombinant Tamm-Horsfall Glycoprotein.
    Kidney international, 1997
    Co-Authors: Nadia Malagolini, Daniela Cavallone, Franca Serafini-cessi
    Abstract:

    Intracellular transport, cell-surface exposure and release of recombinant Tamm-Horsfall Glycoprotein. Human Tamm-Horsfall Glycoprotein (T-H), first described as the major urinary Glycoprotein, is a glycosylphosphatidyl-inositol (GPI)-anchored membrane protein which mainly resides at the luminal face of cells of the thick ascending limb of Henle's loop (TAL) and early distal convoluted tubules of nephron. Since no human renal cell-line producing T-H is available, T-H cDNA was transfected in HeLa cells and a cell line was selected in which 95% of the cells stably expressed T-H, in order to elucidate the biosynthesis, mechanisms regulating the transport of T-H along the exocytic pathway, exposure at the cell surface and release in soluble form. Treatment of cells with an exogenous reducing agent results in a drastic delay in the conversion from precursor to mature T-H. Since the accumulating T-H-precursor carries glycans not yet processed by Golgi-mannosidases, we propose that the formation of a correct set of intrachain disulphide bonds is required for T-H exit out the endoplasmic reticulum. Even the treatment of cells with an inhibitor of GPI-anchor biosynthesis results in an intracellular accumulation of T-H precursor, loss of T-H localization into Golgi apparatus and reduced surface exposure. These results indicate that the GPI-anchor addition is necessary for T-H delivery to the cell-surface. The release rate of new synthesized T-H shows an initial lag time very likely depending on the time required for T-H surface exposure. A portion of released T-H appears to contain ethanolamine, a component of GPI anchor, indicating that, at least in HeLa cells, a GPI-specific phospholipase contributes to the T-H release. Exposure of cells to monensin and brefeldin A results in a loss of accumulation of T-H in the Golgi perinuclear region and a reduced delivery to the cell surface. Under monensin treatment an intermediate T-H form non-exposed at the cell surface is released in the medium, indicating that a soluble T-H may be produced inside the cell under conditions that alter the Golgi apparatus. If such an event occurs in polarized kidney cells, a T-H release from the basolateral face may be postulated, inasmuch as the GPI-anchor is an apical sorting signal. Since T-H is a powerful autoantigen, the accumulation of soluble T-H in the interstitium of TAL may cause the formation of immunocomplexes.

Nadia Malagolini - One of the best experts on this subject based on the ideXlab platform.

  • Tamm-Horsfall Glycoprotein: biology and clinical relevance
    American journal of kidney diseases : the official journal of the National Kidney Foundation, 2003
    Co-Authors: Franca Serafini-cessi, Nadia Malagolini, Daniela Cavallone
    Abstract:

    Tamm-Horsfall Glycoprotein (THP) is the most abundant urinary protein in mammals. Urinary excretion occurs by proteolytic cleavage of the large ectodomain of the glycosyl phosphatidylinositol-anchored counterpart exposed at the luminal cell surface of the thick ascending limb of Henle's loop. We describe the physical-chemical structure of human THP and its biosynthesis and interaction with other proteins and leukocytes. The clinical relevance of THP reported here includes: (1) involvement in the pathogenesis of cast nephropathy, urolithiasis, and tubulointerstitial nephritis; (2) abnormalities in urinary excretion in renal diseases; and (3) the recent finding that familial juvenile hyperuricemic nephropathy and autosomal dominant medullary cystic kidney disease 2 arise from mutations of the THP gene. We critically examine the literature on the physiological role and mechanism(s) that promote urinary excretion of THP. Some lines of research deal with the in vitro immunoregulatory activity of THP, termed uromodulin when isolated from urine of pregnant women. However, an immunoregulatory function in vivo has not yet been established. In the most recent literature, there is renewed interest in the capacity of urinary THP to compete efficiently with urothelial cell receptors, such as uroplakins, in adhering to type 1 fimbriated Escherichia coli. This property supports the notion that abundant THP excretion in urine is promoted in the host by selective pressure to obtain an efficient defense against urinary tract infections caused by uropathogenic bacteria.

  • Salt-precipitation method does not isolate to homogeneity Tamm-Horsfall Glycoprotein from urine of proteinuric patients and pregnant women
    Clinical biochemistry, 2002
    Co-Authors: Daniela Cavallone, Nadia Malagolini, Giovanni-maria Frascà, Sergio Stefoni, Franca Serafini-cessi
    Abstract:

    Abstract Objective: Assessment of the degree of purification of Tamm-Horsfall Glycoprotein from anomalous urine. Design and methods: Two methods have been compared: the method of Tamm & Horsfall (T&H method) consisting in the precipitation of THP by the addition to urine of NaCl up to 0.58 mol/L and the filtration of urine through a diatomaceous earth filter (DEF method) in which THP is selectively trapped because of its gelation/aggregation tendency. The purity of THP preparations has been evaluated by SDS-PAGE analysis and Western blotting developed with anti immunoglobulin G (IgG) antibodies and antichorionic gonadotropin antibodies. Results: All THPs isolated by T&H method from proteinuric patients were contaminated by IgG and one of the five preparations from pregnant women even by chorionic gonadotropin. A smaller or no contamination was found in THPs isolated by DEF method. Conclusions: Although albumin is the most abundant protein in the anomalous urine, it never appears in THP preparations. The consistent contamination with IgG of THP prepared by salt precipitation-method might be related to the formation of a stable complex between the two proteins.

  • Mechanism of Release of Urinary Tamm-Horsfall Glycoprotein from the Kidney GPI-Anchored Counterpart☆
    Biochemical and biophysical research communications, 2001
    Co-Authors: Daniela Cavallone, Nadia Malagolini, Franca Serafini-cessi
    Abstract:

    Human Tamm-Horsfall Glycoprotein (THP) is synthesised in the thick ascending limb of Henle and convoluted distal tubules, inserted into luminal cell-surface by the glycosyl-phosphatidylinositol (GPI)-anchor and excreted in urine at a rate of 50-100 mg per day. Up to date there is no indication on the way in which THP is excreted into the urinary fluid. In this study, we examined by Western blotting THP from human kidney in comparison to urinary THP. As expected for a GPI-anchored protein, THP was recovered from the kidney lysate in a Triton X-100 insoluble form, which moved in a sucrose gradient to a zone of low density. The apparent molecular weight of kidney THP appeared greater than that of urinary THP, but no difference in the electrophoretic mobility was observed when the former was subjected to GPI-specific phospholipase-C treatment, strongly suggesting that a proteolytic cleavage at the juxtamembrane-ectodomain of kidney THP is responsible for the urinary excretion.

  • Binding of human neutrophils to cell-surface anchored Tamm-Horsfall Glycoprotein in tubulointerstitial nephritis.
    Kidney international, 1999
    Co-Authors: Daniela Cavallone, Nadia Malagolini, Franca Serafini-cessi
    Abstract:

    Binding of human neutrophils to cell-surface anchored Tamm-Horsfall Glycoprotein in tubulointerstitial nephritis. Background Human Tamm-Horsfall Glycoprotein (T-H) is a glycosylphosphatidylinositol-anchored protein exposed at the surface of distal nephron cells, and urinary T-H is the released soluble counterpart. The latter has been implicated in tubulointerstitial nephritis, and the proinflammatory potential has been related to its ability to bind in vitro human neutrophils (PMNs). We have examined the conditions required for the binding of neutrophils to cell-surface anchored T-H and the consequent effects. Methods A HeLa cell-line derivative permanently transformed with human T-H cDNA and expressing T-H at the cell surface was used throughout the study. The adhesion of PMNs to cells expressing T-H was analyzed by immunofluorescence microscopy before and after the opsonization of cells with anti–T-H antibodies. The oxidative burst induced by adhesion of PMNs to the cells was determined by the activation of myeloperoxidase. Quantitative and qualitative changes in the release of T-H under the adhesion of activated PMNs were determined by dot-blot and Western blot analysis. Results No binding of neutrophils to cell-surface–anchored T-H was observed. On the contrary, the opsonization of cells with anti–T-H antibodies resulted in a dramatic adhesion of neutrophils. Such an adhesion induced the oxidative burst of PMNs and a large increment in the release of T-H, as well as the release of the slightly faster migrating T-H form, which is normally retained intracellularly. Conclusions These results support the notion that, after the autoimmune response, the adhesion of neutrophils to cell-surface T-H contributes to the pathogenesis of tubulointerstitial nephritis, favoring a further accumulation of T-H in the interstitium and inducing the loss of cell integrity via reactive oxygen metabolites generated by activated neutrophils.

  • Intracellular transport, cell-surface exposure and release of recombinant Tamm-Horsfall Glycoprotein.
    Kidney international, 1997
    Co-Authors: Nadia Malagolini, Daniela Cavallone, Franca Serafini-cessi
    Abstract:

    Intracellular transport, cell-surface exposure and release of recombinant Tamm-Horsfall Glycoprotein. Human Tamm-Horsfall Glycoprotein (T-H), first described as the major urinary Glycoprotein, is a glycosylphosphatidyl-inositol (GPI)-anchored membrane protein which mainly resides at the luminal face of cells of the thick ascending limb of Henle's loop (TAL) and early distal convoluted tubules of nephron. Since no human renal cell-line producing T-H is available, T-H cDNA was transfected in HeLa cells and a cell line was selected in which 95% of the cells stably expressed T-H, in order to elucidate the biosynthesis, mechanisms regulating the transport of T-H along the exocytic pathway, exposure at the cell surface and release in soluble form. Treatment of cells with an exogenous reducing agent results in a drastic delay in the conversion from precursor to mature T-H. Since the accumulating T-H-precursor carries glycans not yet processed by Golgi-mannosidases, we propose that the formation of a correct set of intrachain disulphide bonds is required for T-H exit out the endoplasmic reticulum. Even the treatment of cells with an inhibitor of GPI-anchor biosynthesis results in an intracellular accumulation of T-H precursor, loss of T-H localization into Golgi apparatus and reduced surface exposure. These results indicate that the GPI-anchor addition is necessary for T-H delivery to the cell-surface. The release rate of new synthesized T-H shows an initial lag time very likely depending on the time required for T-H surface exposure. A portion of released T-H appears to contain ethanolamine, a component of GPI anchor, indicating that, at least in HeLa cells, a GPI-specific phospholipase contributes to the T-H release. Exposure of cells to monensin and brefeldin A results in a loss of accumulation of T-H in the Golgi perinuclear region and a reduced delivery to the cell surface. Under monensin treatment an intermediate T-H form non-exposed at the cell surface is released in the medium, indicating that a soluble T-H may be produced inside the cell under conditions that alter the Golgi apparatus. If such an event occurs in polarized kidney cells, a T-H release from the basolateral face may be postulated, inasmuch as the GPI-anchor is an apical sorting signal. Since T-H is a powerful autoantigen, the accumulation of soluble T-H in the interstitium of TAL may cause the formation of immunocomplexes.

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