title: Platelet involvement in experimental immune complex-mediated glomerulonephritis in the nonhuman primate.
abstract: Abundant glomerular platelet deposition is a hallmark of certain animal models of immune complex (IC)-mediated glomerulonephritis (GN). By contrast, conspicuous platelet deposition is uncommon in the IC-GN seen in humans. This could result from intrinsic differences between human and animal platelets, which are known to be present. To assess whether abundant glomerular platelet deposition can occur in humans with IC-GN, the present studies were undertaken in nonhuman primates (cynomolgus monkeys, CYN), with active experimental IC-GN induced by 12 weeks of daily intravenous infusion of bovine gamma globulin (BGG). CYN are appropriate for these studies because, like humans, CYN platelets do not express the C3b receptor but do express receptors for the Fc region of IgG (FcR gamma II). Furthermore, in this model of IC-GN, which is indistinguishable from IC-GN seen in humans, it is possible to time the biopsy to coincide with a period of peak activity of the GN. The present studies proceeded as follows: ten CYN were studied before and after intravenous infusion of BGG sufficient to achieve conditions near antigen/antibody equivalence for circulating precipitating antibody to BGG. The infusion of BGG, which was given over 10 minutes, resulted in an acute reduction in circulating platelets (mean 43% +/- 5 SE, P < 0.001). However, renal biopsies performed before and five minutes after the acute reduction in circulating platelets showed that relatively few of the platelets removed from the circulation lodged in glomeruli (platelets/glomerular cross section: 0.2 +/- 0.06 before BGG vs. 0.88 +/- 0.31 after BGG, P = 0.035). In five of the CYN studied under the above protocol, autologous platelets were labeled with 111In and reinfused into the CYN just prior to the BGG infusion. These studies confirmed the paucity of platelet deposition in kidney but showed major uptake of the 111In-labeled platelets by liver and spleen (mean +/- SE 111In CPM/mg of tissue: kidney cortex 18 +/- 8, liver 132 +/- 42, and spleen 808 +/- 127, P = 0.038, comparing kidney to liver or spleen by paired t-test). Thus, the platelets removed from the circulation were taken up at the sites which are also the principal sites of IC uptake (liver and spleen), and over the time interval that coincides with the period of maximum uptake of IC by liver and spleen, after BGG infusion. In vitro studies, discussed herein, showed that BGG anti-BGG IC bind to CYN platelets via FcR gamma II.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus.
authors.forename: J D
authors.initials: JD
authors.lastname: Mahan
authors.forename: L A
authors.initials: LA
authors.lastname: Hebert
authors.forename: C
authors.initials: C
authors.lastname: McAllister
authors.forename: D J
authors.initials: DJ
authors.lastname: Birmingham
authors.forename: X P
authors.initials: XP
authors.lastname: Shen
authors.forename: F G
authors.initials: FG
authors.lastname: Cosio
authors.forename: J
authors.initials: J
authors.lastname: Brandt
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D002417:Cattle; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D008854:Microscopy, Electron; D005719:gamma-Globulins / Q000494:pharmacology
chemical_list: D000936:Antigen-Antibody Complex; D005719:gamma-Globulins