Platelet cationic proteins are present in glomeruli of lupus nephritis patients

G. Camussi, C. Tetta, G. Mazzucco, G. Monga, C. Roffinello, M. Alberton, P. Dellabona, F. Malavasi, A. Vercellone

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Synthetic polycations have been shown to bind and neutralize glomerular polyanions (GPA), thereby increasing the permeability of the glomerular capillary wall (GCW). In the present study it is demonstrated that human platelet-derived cationic proteins (HuPlt CP), which are able to increase cutaneous vascular permeability, bind in vitro to the GCW following incubation of normal human kidney sections with purified HuPlt CP or with washed human platelets stimulated with thrombin, immune complexes (IC) and platelet-activating factor (PAF), or stimulated with a suspension of washed human platelets and polymorphonuclear leukocytes in the presence of phagocytable substrate. The antiserum used in immunofluorescence test to detect the binding of HuPlt CP was specific for two different molecular types of HuPlt CP, both with an isoelectric point (pI) of 10.5. Glomerular deposits of HuPlt CP were also detectable by immunofluorescence microscopy in renal glomeruli present in tissue obtained by biopsy from patients with systemic lupus erythematosus (SLE), a disease in which platelets have been implicated as mediator of glomerular injury. These data indicate that when activated platelets release HuPlt CP in vivo, these proteins bind to glomerular structures. The binding of HuPlt CP to GCW appears to be ionic in nature since heparin, a polyanion, prevents this binding in vitro. In addition, heparin, as well as a high molarity buffer, removed deposits of HuPlt CP bound in vitro to normal GCW or bound in vivo to glomeruli of patients with SLE. The binding of HuPlt CP to GCW is associated with loss of colloidal iron staining, a qualitative technique that demonstrates primarily epithelial cell surface anionic sialoglycoproteins. In experiments of in vitro binding of purified HuPlt CP to section of normal kidney treatment with heparin completely restores the normal pattern of colloidal iron staining suggesting ionic neutralization of GPA. In contrast, heparin is only partially effective in restoring colloidal iron staining in normal kidney sections treated with platelets directly stimulated with IC or PAF or in kidney sections of patients with SLE. These observations indicate that under these conditions the ionic interaction of HuPlt CP with GCW is only partially responsible for the loss of colloidal iron staining. The results of the present study suggest that biologically active polycationic mediators released from stimulated platelets localize in GCW and participate in the induction of glomerular injury.

Original languageEnglish
Pages (from-to)555-565
Number of pages11
JournalKidney International
Volume30
Issue number4
Publication statusPublished - 1986

Fingerprint

Lupus Nephritis
Blood Platelets
Proteins
Heparin
Kidney
Iron
Systemic Lupus Erythematosus
Staining and Labeling
Platelet Activating Factor
Capillary Permeability
Antigen-Antibody Complex
Sialoglycoproteins
Wounds and Injuries
Isoelectric Point

ASJC Scopus subject areas

  • Nephrology

Cite this

Camussi, G., Tetta, C., Mazzucco, G., Monga, G., Roffinello, C., Alberton, M., ... Vercellone, A. (1986). Platelet cationic proteins are present in glomeruli of lupus nephritis patients. Kidney International, 30(4), 555-565.

Platelet cationic proteins are present in glomeruli of lupus nephritis patients. / Camussi, G.; Tetta, C.; Mazzucco, G.; Monga, G.; Roffinello, C.; Alberton, M.; Dellabona, P.; Malavasi, F.; Vercellone, A.

In: Kidney International, Vol. 30, No. 4, 1986, p. 555-565.

Research output: Contribution to journalArticle

Camussi, G, Tetta, C, Mazzucco, G, Monga, G, Roffinello, C, Alberton, M, Dellabona, P, Malavasi, F & Vercellone, A 1986, 'Platelet cationic proteins are present in glomeruli of lupus nephritis patients', Kidney International, vol. 30, no. 4, pp. 555-565.
Camussi G, Tetta C, Mazzucco G, Monga G, Roffinello C, Alberton M et al. Platelet cationic proteins are present in glomeruli of lupus nephritis patients. Kidney International. 1986;30(4):555-565.
Camussi, G. ; Tetta, C. ; Mazzucco, G. ; Monga, G. ; Roffinello, C. ; Alberton, M. ; Dellabona, P. ; Malavasi, F. ; Vercellone, A. / Platelet cationic proteins are present in glomeruli of lupus nephritis patients. In: Kidney International. 1986 ; Vol. 30, No. 4. pp. 555-565.
@article{4e296dee616b458ab8a003f08f970ca6,
title = "Platelet cationic proteins are present in glomeruli of lupus nephritis patients",
abstract = "Synthetic polycations have been shown to bind and neutralize glomerular polyanions (GPA), thereby increasing the permeability of the glomerular capillary wall (GCW). In the present study it is demonstrated that human platelet-derived cationic proteins (HuPlt CP), which are able to increase cutaneous vascular permeability, bind in vitro to the GCW following incubation of normal human kidney sections with purified HuPlt CP or with washed human platelets stimulated with thrombin, immune complexes (IC) and platelet-activating factor (PAF), or stimulated with a suspension of washed human platelets and polymorphonuclear leukocytes in the presence of phagocytable substrate. The antiserum used in immunofluorescence test to detect the binding of HuPlt CP was specific for two different molecular types of HuPlt CP, both with an isoelectric point (pI) of 10.5. Glomerular deposits of HuPlt CP were also detectable by immunofluorescence microscopy in renal glomeruli present in tissue obtained by biopsy from patients with systemic lupus erythematosus (SLE), a disease in which platelets have been implicated as mediator of glomerular injury. These data indicate that when activated platelets release HuPlt CP in vivo, these proteins bind to glomerular structures. The binding of HuPlt CP to GCW appears to be ionic in nature since heparin, a polyanion, prevents this binding in vitro. In addition, heparin, as well as a high molarity buffer, removed deposits of HuPlt CP bound in vitro to normal GCW or bound in vivo to glomeruli of patients with SLE. The binding of HuPlt CP to GCW is associated with loss of colloidal iron staining, a qualitative technique that demonstrates primarily epithelial cell surface anionic sialoglycoproteins. In experiments of in vitro binding of purified HuPlt CP to section of normal kidney treatment with heparin completely restores the normal pattern of colloidal iron staining suggesting ionic neutralization of GPA. In contrast, heparin is only partially effective in restoring colloidal iron staining in normal kidney sections treated with platelets directly stimulated with IC or PAF or in kidney sections of patients with SLE. These observations indicate that under these conditions the ionic interaction of HuPlt CP with GCW is only partially responsible for the loss of colloidal iron staining. The results of the present study suggest that biologically active polycationic mediators released from stimulated platelets localize in GCW and participate in the induction of glomerular injury.",
author = "G. Camussi and C. Tetta and G. Mazzucco and G. Monga and C. Roffinello and M. Alberton and P. Dellabona and F. Malavasi and A. Vercellone",
year = "1986",
language = "English",
volume = "30",
pages = "555--565",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Platelet cationic proteins are present in glomeruli of lupus nephritis patients

AU - Camussi, G.

AU - Tetta, C.

AU - Mazzucco, G.

AU - Monga, G.

AU - Roffinello, C.

AU - Alberton, M.

AU - Dellabona, P.

AU - Malavasi, F.

AU - Vercellone, A.

PY - 1986

Y1 - 1986

N2 - Synthetic polycations have been shown to bind and neutralize glomerular polyanions (GPA), thereby increasing the permeability of the glomerular capillary wall (GCW). In the present study it is demonstrated that human platelet-derived cationic proteins (HuPlt CP), which are able to increase cutaneous vascular permeability, bind in vitro to the GCW following incubation of normal human kidney sections with purified HuPlt CP or with washed human platelets stimulated with thrombin, immune complexes (IC) and platelet-activating factor (PAF), or stimulated with a suspension of washed human platelets and polymorphonuclear leukocytes in the presence of phagocytable substrate. The antiserum used in immunofluorescence test to detect the binding of HuPlt CP was specific for two different molecular types of HuPlt CP, both with an isoelectric point (pI) of 10.5. Glomerular deposits of HuPlt CP were also detectable by immunofluorescence microscopy in renal glomeruli present in tissue obtained by biopsy from patients with systemic lupus erythematosus (SLE), a disease in which platelets have been implicated as mediator of glomerular injury. These data indicate that when activated platelets release HuPlt CP in vivo, these proteins bind to glomerular structures. The binding of HuPlt CP to GCW appears to be ionic in nature since heparin, a polyanion, prevents this binding in vitro. In addition, heparin, as well as a high molarity buffer, removed deposits of HuPlt CP bound in vitro to normal GCW or bound in vivo to glomeruli of patients with SLE. The binding of HuPlt CP to GCW is associated with loss of colloidal iron staining, a qualitative technique that demonstrates primarily epithelial cell surface anionic sialoglycoproteins. In experiments of in vitro binding of purified HuPlt CP to section of normal kidney treatment with heparin completely restores the normal pattern of colloidal iron staining suggesting ionic neutralization of GPA. In contrast, heparin is only partially effective in restoring colloidal iron staining in normal kidney sections treated with platelets directly stimulated with IC or PAF or in kidney sections of patients with SLE. These observations indicate that under these conditions the ionic interaction of HuPlt CP with GCW is only partially responsible for the loss of colloidal iron staining. The results of the present study suggest that biologically active polycationic mediators released from stimulated platelets localize in GCW and participate in the induction of glomerular injury.

AB - Synthetic polycations have been shown to bind and neutralize glomerular polyanions (GPA), thereby increasing the permeability of the glomerular capillary wall (GCW). In the present study it is demonstrated that human platelet-derived cationic proteins (HuPlt CP), which are able to increase cutaneous vascular permeability, bind in vitro to the GCW following incubation of normal human kidney sections with purified HuPlt CP or with washed human platelets stimulated with thrombin, immune complexes (IC) and platelet-activating factor (PAF), or stimulated with a suspension of washed human platelets and polymorphonuclear leukocytes in the presence of phagocytable substrate. The antiserum used in immunofluorescence test to detect the binding of HuPlt CP was specific for two different molecular types of HuPlt CP, both with an isoelectric point (pI) of 10.5. Glomerular deposits of HuPlt CP were also detectable by immunofluorescence microscopy in renal glomeruli present in tissue obtained by biopsy from patients with systemic lupus erythematosus (SLE), a disease in which platelets have been implicated as mediator of glomerular injury. These data indicate that when activated platelets release HuPlt CP in vivo, these proteins bind to glomerular structures. The binding of HuPlt CP to GCW appears to be ionic in nature since heparin, a polyanion, prevents this binding in vitro. In addition, heparin, as well as a high molarity buffer, removed deposits of HuPlt CP bound in vitro to normal GCW or bound in vivo to glomeruli of patients with SLE. The binding of HuPlt CP to GCW is associated with loss of colloidal iron staining, a qualitative technique that demonstrates primarily epithelial cell surface anionic sialoglycoproteins. In experiments of in vitro binding of purified HuPlt CP to section of normal kidney treatment with heparin completely restores the normal pattern of colloidal iron staining suggesting ionic neutralization of GPA. In contrast, heparin is only partially effective in restoring colloidal iron staining in normal kidney sections treated with platelets directly stimulated with IC or PAF or in kidney sections of patients with SLE. These observations indicate that under these conditions the ionic interaction of HuPlt CP with GCW is only partially responsible for the loss of colloidal iron staining. The results of the present study suggest that biologically active polycationic mediators released from stimulated platelets localize in GCW and participate in the induction of glomerular injury.

UR - http://www.scopus.com/inward/record.url?scp=0022546661&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022546661&partnerID=8YFLogxK

M3 - Article

C2 - 3784294

AN - SCOPUS:0022546661

VL - 30

SP - 555

EP - 565

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 4

ER -