The pentraxins, C-reactive protein and serum amyloid P component, are cleared and catabolized by hepatocytes in vivo.
The cellular sites of clearance and degradation of the pentraxin plasma proteins, C-reactive protein, the classical acute phase reactant, and serum amyloid P component (SAP), a universal constituent of amyloid deposits, were sought using the ligand 125I-tyramine cellobiose (TC) which is substantially retained within the cells in which catabolism takes place. Pentraxins labeled with 125I-TC showed the same in vitro and in vivo ligand binding and the same in vivo plasma t1/2 as the directly iodinated proteins and the native unlabeled pentraxins, indicating that their mode of clearance was likely to be physiological. After intravenous injection into mice and rabbits of human C-reactive protein, human SAP, and mouse SAP, each labeled with 125I-TC, most of the radioactivity remaining in the body at 24 h was located in hepatocytes. None was detected in other liver cells, and only traces were present in other viscera; the rest was in the carcass, representing intact pentraxins in the blood and extravascular compartment, and escaped label which had not yet been excreted. Hepatocytes are thus the single major site of pentraxin clearance and catabolism in vivo. This is consistent with the observation that SAP that has localized to amyloid deposits persists there and is not degraded.
Hutchinson
W L
WL
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Noble
G E
GE
Hawkins
P N
PN
Pepys
M B
MB
D000818:Animals; D002097:C-Reactive Protein / Q000008:administration & dosage / Q000378:metabolism*; D002475:Cellobiose; D005260:Female; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D009928:Organ Specificity; D011817:Rabbits; D000683:Serum Amyloid P-Component / Q000008:administration & dosage / Q000378:metabolism*; D014439:Tyramine
D000683:Serum Amyloid P-Component; C038394:tyramine-cellobiose adduct; D002475:Cellobiose; D002097:C-Reactive Protein; D014439:Tyramine