Immunolocalization of lipid peroxidation/advanced glycation end products in amyloid A amyloidosis.
Chronic inflammation, superimposed by amyloid fibril deposition, is believed to trigger the cascade of oxidative stress response in the affected organs and tissues. We examined immunohistochemically the distribution of 4-hydroxy-2-nonenal (HNE) and N(epsilon)-(carboxymethyl)lysine (CML), markers of lipid peroxidation and advance glycation end products (AGE), respectively, in spleen sections and peritoneal macrophages (MPhi) from mice before and during AA amyloidosis. With time, both HNE and CML immunoreactivities increased significantly in MPhi and splenic reticuloendothelial cells, known to be associated with the clearance of serum amyloid A, the precursor of AA fibrils. HNE and CML were localized to the plasma membrane and the cytoplasmic compartment of MPhi and HNE only at the nuclear membrane. These markers were also colocalized bound to AA fibrils infiltrating the splenic sinus walls. Our results reinforce the notion that oxidative stress is an integral component of amyloidotic tissues. Both lipid peroxidation and AGE have been implicated in protein modification and amyloid fibril formation. The significance of HNE and CML associated with the monocytoid cells and implicated in SAA clearance and AA fibril formation, is discussed with the pathogenesis of AA fibrils.
Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3A 2B4, Canada.
Golnar
G
Kamalvand
Zafer
Z
Ali-Khan
D000447:Aldehydes / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D004443:Echinococcosis / Q000469:parasitology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009685:Nuclear Envelope / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000276:immunology / Q000502:physiology; D058225:Plaque, Amyloid / Q000473:pathology; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013154:Spleen / Q000378:metabolism* / Q000473:pathology
D000447:Aldehydes; D017127:Glycation End Products, Advanced; D000685:Serum Amyloid A Protein; C027576:4-hydroxy-2-nonenal