Laboratory Investigation

Kidney International (1984) 25, 759–765; doi:10.1038/ki.1984.87

Binding of platelet factor four (PF 4) to glomerular polyanion

Jeffrey L Barnes1, Shirley P Levine1 and Manjeri A Venkatachalam1

1Departments of Pathology and Medicine, University of Texas Health Science Center and Audie Murphy Veterans Administration Hospital, San Antonio, Texas

Correspondence: Dr J L Barnes, Department of Pathology, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284, USA

Received 25 May 1983; Revised 13 October 1983.

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Abstract

Binding of platelet factor four (PF 4) to glomerular polyanion. Synthetic polycations have been shown to bind to glomerular polyanion (GPA) and increase glomerular permeability. Here, we show that human platelet factor 4 (PF 4), a platelet secretory protein, binds to GPA. The following methods were used to assess PF 4 binding to GPA: (1) Sections of human and rat renal cortex were incubated with PF 4 or PF 4 was injected intravenously into rats followed by immunofluorescence techniques; (2) 125I-PF 4 was added to isolated glomerular basement membrane (GBM) suspensions and binding assessed isotopically; (3) PF 4 was perfused through rat kidneys ex vivo followed by immunoper-oxidase methods for electron microscopy (EM). In vitro and in vivo, PF 4 bound to the mesangium and linearly to capillary walls. Isotopic studies showed dose-dependent saturable binding of PF 4 to GBM which was reversed by heparin. By EM, PF 4 binding sites were resolved in the GBM, particularly in the laminae rarae as punctate densities similar in distribution to anionic sites revealed by cationic dyes. Also, endothelial and epithelial cell surfaces stained. An ionic interaction between PF 4 and GPA was indicated by elimination of staining by washing PF 4-treated sections with buffer containing 1.0 and 3.0 M NaCl or with heparin. Pretreatment of rats with polyethylenei-mine (a synthetic polycation) blocked PF 4 binding. Heparin administration in vivo removed previously bound PF 4. By virtue of its affinity for GPA and behavior like a polycation, PF 4 may alter glomerular permeability and play a role in glomerular disease.

Liaison du facteur plaquettaire quatre (PF 4) aux polyanions glomérulaires. Il a été démontré que des polycations synthétiques se lient aux polyanions glomérulaires (GPA) et augmentent la perméabilité glomérulaire. Ici, nous montrons que le facteur plaquettaire 4 (PF 4), une protéine sécrétoire plaquettaire, se lie au GPA. Les méthodes suivantes ont été utilisées pour préciser la liaison du PF 4 au GPA: (1) Des sections de cortex de reins d'homme et de rat ont été incubées avec du PF 4, ou le PF 4 a été injecté par voie intraveineuse à des rats, avec ensuite techniques d'immunofluorescence; (2) 125I-PF 4 a été ajouté à des suspensions de membranes basales glomérulaires isolées (GBM) et la liaison mesurée de façon isotopique; (3) le PF 4 a été perfusé à des reins de rat ex-vivo avec ensuite technique d'immunoperoxidase pour microscopie électronique (EM). In vitro et in vivo, le PF 4 se liait au mésangium, et de façon linéaire aux parois capillaires. Des études isotopiques ont montré une liaison saturable, dose dépendante, du PF 4 aux GBM, qui était réversible par de l'héparine. En EM, les sites de liaison du PF 4 étaient visibles sur la GBM, surtout sur les laminae rarae, sous forme de densifications ponctuées, identiques aux sites de distribution anionique révélés par les colorants cationiques. Egalement, les surfaces cellulaires endothélials et épithéliales étaient colorées. Une interaction ionique entre PF 4 et GPA était indiquée par l'élimination de la coloration en lavant des sections traitées au PF 4 avec un tampon contenant 1,0 ou 3,0 M NaCl, ou avec de l'héparine. Le prétraitement de rats avec du polyéthylènimine (un polycation synthétique) a bloqué la liaison du PF 4. L'administration d'héparine in-vivo a enlevé le PF 4 préalablement lié. En raison de son affinité pour le PGA, et de son comportement comme un polycation, PF 4 pourrait altérer la perméabilité glomérulaire et jouer un rôle dans les glomérulopathies.

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