The putative role of alpha-1-antitrypsin in the disaggregation of amyloid lambda fibrils.
OBJECTIVE
Interactions between hydrophobic compounds like cholesterol and lithocholic acid and alpha-1-antitrypsin (alpha-1-AT) have previously been described. We studied the putative interaction between alpha-1-AT and the insoluble, hydrophobic, beta-pleated sheet, light-chain-derived fibrils that predominate the tissue deposits in primary immunocytic (AL) related amyloidosis.


METHODS
Amyloid fibrils were isolated from two cases with lambda and two cases with kappa AL amyloidosis.


RESULTS
The lambda fibrils could be completely disaggregated (as shown by light and electron microscopy and Congo red uptake) by alpha-1-AT added in the molar ratio 1:5, whereas fibrils with predominantly kappa chains remained unaffected. The lambda-chain interaction was accompanied by characteristic changes of the physicochemical and biological properties of alpha-1-AT apparent in an increased thermal stability and loss of elastase-inhibitory activity. These findings are compatible with a transition of alpha-1-AT from a native, stressed conformation to a relaxed form.


CONCLUSIONS
Disaggregation of lambda AL amyloid fibrils can be achieved by addition of alpha-1-AT. The findings may have therapeutic implications in primary amyloidosis.
Department of Medicine, Lund University, Malmö General Hospital, Sweden.
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S
Eriksson
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Janciauskiene
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G
Merlini
D000368:Aged; D000682:Amyloid / Q000648:ultrastructure*; D000686:Amyloidosis / Q000473:pathology*; D015153:Blotting, Western; D004586:Electrophoresis; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D000515:alpha 1-Antitrypsin / Q000648:ultrastructure*
D000682:Amyloid; D000515:alpha 1-Antitrypsin