Binding, trafficking and accumulation of serum amyloid A in peritoneal macrophages.

Abstract:

:Murine serum amyloid A1.1 (SAA1.1) has been conjugated with the fluorophore Texas Red (TxR), and its interaction with peritoneal macrophages has been visualized by scanning confocal microscopy. Binding of TxR-SAA to cell surfaces was inhibited by an excess of unlabelled SAA indicating the involvement of saturable receptors. Internalized TxR-SAA was seen initially as small punctate signals which in some cells evolved into a fine fluorescent network, a pattern typical of tubular endosomes. Colocalization of TxR-SAA with Cy5-labelled low density lipoprotein (LDL) but not with Oregon Green-labelled transferrin suggested that SAA trafficked through endosomes and lysosomes for degradation rather than through recycling compartments. Consistent with this catabolic pathway, macrophages loaded with TxR-SAA lost fluorescence within several days after being shifted to a fluorophore-free medium. In sharp contrast to this, cells maintained under amyloid-forming conditions, i.e. in the presence of unlabelled SAA and amyloid-enhancing factor (AEF) before and after treatment with TxR-SAA, remained brightly fluorescent over the course of 5 days. Immunocytochemistry verified the accumulation of SAA within macrophages. These findings support the hypothesis that a decreased catabolism of internalized SAA plays a role in AA amyloid pathogenesis.

journal_name

Scand J Immunol

authors

Kluve-Beckerman B,Manaloor J,Liepnieks JJ

doi

10.1046/j.1365-3083.2001.00879.x

keywords:

subject

Has Abstract

pub_date

2001-04-01 00:00:00

pages

393-400

issue

4

eissn

0300-9475

issn

1365-3083

pii

sji879

journal_volume

53

pub_type

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