title: In situ expression and soluble form of P-selectin in human glomerulonephritis.
abstract: To clarify the early involvement of cellular adhesion molecules in human glomerulonephritis, we investigated P-selectin and high endothelial venules' (HEVs) marker MECA-79 expression in kidney specimens by immunohistochemical and in situ hybridization analyses, and measured serum and urinary soluble P-selectin levels by enzyme-linked immunosorbent assay. In normal controls, P-selectin and MECA-79 expression were negative in glomeruli (N = 4), and serum soluble P-selectin levels were 114.3 +/- 36.8 ng/ml (mean +/- SEM, N = 12). Soluble P-selectin was not detectable in urine of all cases. In proliferative glomerulonephritis involving rapidly progressive glomerulonephritis (N = 6), IgA nephropathy (N = 26), lupus nephritis (N = 7) and acute glomerulonephritis (N = 2), both glomerular and interstitial P-selectin expression were up-regulated. Glomerular P-selectin expression correlated positively with local cellular accumulation, endocapillary proliferation and CD41b (platelet) staining. Interstitial P-selectin expression showed a positive correlation with the grade of local cellular infiltrates. P-selectin mRNA signals detected by in situ hybridization were only observed on capillary or venous endothelium in the interstitium, but not in glomeruli. In addition, MECA-79 was expressed on the plump endothelial cells at the cortico-medullary junction (outer medulla). Serum soluble P-selectin levels were significantly higher in patients with proliferative glomerulonephritis, especially in glomerular and interstitial P-selectin positive staining, and correlated with glomerular endocapillary proliferation. These observations suggested that P-selectin was associated with both glomerular and interstitial leukocyte accumulation in human glomerulonephritis, and might be expressed by two distinct mechanisms that are the activated platelets in glomeruli and the de novo expression in the interstitial lesions that correlated with MECA-79 expression as HEVs like vessels, and serum soluble P-selectin may be a useful marker for predicting in situ P-selectin expression associated with glomerular endocapillary proliferation in nephritis.
authors.affiliation: First Department of Internal Medicine, School of Medicine, Kanazawa University, Ishikawa, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Segawa
authors.forename: T
authors.initials: T
authors.lastname: Wada
authors.forename: M
authors.initials: M
authors.lastname: Takaeda
authors.forename: K
authors.initials: K
authors.lastname: Furuichi
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Hisada
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: K
authors.initials: K
authors.lastname: Takasawa
authors.forename: S
authors.initials: S
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D019007:P-Selectin / Q000737:chemistry / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D000954:Antigens, Surface; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex