The ICAM-1/LFA-1 interaction in glomerular leukocytic accumulation in anti-GBM glomerulonephritis.
Recent studies of rat anti-glomerular basement membrane (anti-GBM) disease have demonstrated a functional role for ICAM-1 in the entry of leukocytes into the glomerulus, both in the early polymorphonuclear (PMNL) influx and the more delayed monocyte/macrophage infiltration. In the current study we used immunogold ultrastructural techniques to identify the exact sites of expression of ICAM-1 (CD54) in the glomerulus and the expression of CD11a and CD18 by infiltrating glomerular leukocytes in the first 24 hours of accelerated anti-GBM disease in rats. In normal rats there was constitutive ICAM-1 expression on the luminal surface of the glomerular endothelium and parietal epithelium of Bowman's capsule. In disease ICAM-1 expression was progressively increased over 24 hours on a thickened, reactive glomerular endothelium, being most prominent on endothelium adjacent to the mesangial stalks. Mesangial cells demonstrated surface ICAM-1 expression only in focal areas of superficial mesangiolysis. PMNL, the predominant glomerular inflammatory cell in the first 12 hours of accelerated anti-GBM GN, expressed abundant surface CD18 which was present at the sites of adhesion of the PMNL to the glomerular endothelium. In contrast PMNL expressed only very sparse surface CD11a, suggesting that another beta 2 integrin, Mac-1, which shares a common beta chain with LFA-1 may be the more important PMNL counter receptor for ICAM-1 in the glomerulus. Glomerular monocyte/macrophage infiltration became evident within glomerular capillary loops and the mesangium from 6 to 24 hours. These adherent and migrating leukocytes expressed abundant surface CD11a and moderate CD18 particularly at their sites of adhesion to glomerular endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Hill
P A
PA
Department of Anatomy, University of Melbourne, Parkville, Australia.
Lan
H Y
HY
Nikolic-Paterson
D J
DJ
Atkins
R C
RC
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001485:Basement Membrane / Q000378:metabolism* / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1; D007962:Leukocytes / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008297:Male; D016253:Microscopy, Immunoelectron; D051381:Rats; D017207:Rats, Sprague-Dawley
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1