The pentraxins, C-reactive protein and serum amyloid P component, are cleared and catabolized by hepatocytes in vivo.

Abstract

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 'MI-yramine cellobiose (TC) which is substantially retained within the cells in which catabolism takes place. Pentraxins labeled with '"I-TC showed the same in vitro and in vivo ligand binding and the same in vivo plasma to 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 '"I-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. (J. CliU. Invest. 1994. 94:1390-1396

C-Reactive Protein: Eighty Years from Discovery to Emergence as a Major Risk Marker for Cardiovascular Disease

“…They and other investigators further demonstrated that the bulk of circulating CRP is produced by hepatocytes largely under regulatory control of inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-␣; that the plasma half-life of CRP is approximately 19 h under basal and stress conditions; and thus that the plasma concentration is largely determined by synthetic rate (14,15 ).…”

Molecular dissection of Alzheimer's disease neuropathology by depletion of serum amyloid P component

“…injection into mice, compared to the Ϸ3-h plasma half-life of native human SAP in mice (26). Circulating SAP is normally cleared in vivo exclusively by hepatocytes (26) but not via the asialoglycoprotein receptor (27) and the rapid clearance of the SAP-CPHPC complex in mice was also not affected by concurrent administration of desialylated orosomucoid to block this receptor (27). Circular dichroism measurements showed no significant secondary or tertiary structural change in the SAP-CPHPC complex compared to native SAP alone (Fig.…”

Transgenic human C-reactive protein is not proatherogenic in apolipoprotein E-deficient mice

“…The plasma clearance rates of 125 I-human CRP, after i.v. injection into groups of age-matched male apoE Ϫ/Ϫ -hCRP ϩ and apoE Ϫ/Ϫ mice, were measured exactly as described (36).…”