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AA-amyloidosis can be transferred by peripheral blood monocytes.

Sponarova J, Nyström SN, Westermark GT - PLoS ONE (2008)

Bottom Line: The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not be expressed by the monocytes.Plasma recovered from mice with AA amyloidosis lacked seeding capacity.Human AA-amyloidosis resembles the murine form and every individual is expected to be exposed to conditions that initiate production of the acute-phase reactant.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

ABSTRACT
Spongiform encephalopathies have been reported to be transmitted by blood transfusion even prior to the clinical onset. Experimental AA-amyloidosis shows similarities with prion disease and amyloid-containing organ-extracts can prime a recipient for the disease. In this systemic form of amyloidosis N-terminal fragments of the acute-phase reactant apolipoprotein serum amyloid A are the main amyloid protein. Initial amyloid deposits appear in the perifollicular region of the spleen, followed by deposits in the liver. We used the established murine model and induced AA-amyloidosis in NMRI mice by intravenous injections of purified amyloid fibrils ('amyloid enhancing factor') combined with inflammatory challenge (silver nitrate subcutaneously). Blood plasma and peripheral blood monocytes were isolated, sonicated and re-injected into new recipients followed by an inflammatory challenge during a three week period. When the animals were sacrificed presence of amyloid was analyzed in spleen sections after Congo red staining. Our result shows that some of the peripheral blood monocytes, isolated from animals with detectable amyloid, contained amyloid-seed that primed for AA-amyloid. The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not be expressed by the monocytes. Plasma recovered from mice with AA amyloidosis lacked seeding capacity. Amyloid enhancing activity can reside in monocytes recovered from mice with AA-amyloidosis and in a prion-like way trigger amyloid formation in conjunction with an inflammatory disorder. Human AA-amyloidosis resembles the murine form and every individual is expected to be exposed to conditions that initiate production of the acute-phase reactant. The monocyte-transfer mechanism should be eligible for the human disease and we point out blood transfusion as a putative route for transfer of amyloidosis.

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Spleen amyloid deposits stained with Congo red.(A) The amyloid appears pink and is localized to the perifollicular zone. (B) The identical area exhibits green birefringence in polarized light. Amyloid is indicated by arrows.
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pone-0003308-g001: Spleen amyloid deposits stained with Congo red.(A) The amyloid appears pink and is localized to the perifollicular zone. (B) The identical area exhibits green birefringence in polarized light. Amyloid is indicated by arrows.

Mentions: The study continued with analysis of the possibility that peripheral blood monocytes carry amyloid seeds. Profound amounts of amyloid developed in spleen of group G mice after given AEF and 5 weekly AgNO3 injections. Isolated and sonicated peripheral blood monocytes from group G mice were re-injected into new mice (H1-9). Inflammatory stimuli were given to mice in the groups H1-8. These groups varied in size and contained 5–8 animals (Table 2). After Congo red staining, amyloid deposits were detected in 19/48 (40%) of the recipient mice. The amyloid was present in the perifollicular area of the white pulp, and ranged from traces up to moderate amount (1+ to 3+) (Figure 1). The percentage of affected animals differed between groups and in group H2 all mice developed amyloid while this was absent in mice from group H5 and H7 (Table 3). The five animals in group H9 received monocytes isolated from G9 without the concomitant inflammatory stimuli (group H9), and no amyloid developed. Peripheral blood monocytes were also isolated from healthy animals and after sonication injected into nine mice (H10) which received the concomitant inflammatory stimuli. Also in these mice amyloid was absent (Table 2). To validate this phenomenon, peripheral blood monocytes were isolated from the five mice of group H2 that developed AA-amyloid deposits triggered by sonicated peripheral blood monocytes and AgNO3 injections. The isolated monocytes were after sonication reinjected into new groups of healthy mice (groups J1–J5) and AgNO3 was administered as before. Indeed, after 16 days amyloid was present in 80% (12/15) of the animals in group J 1–5. The degree of amyloid ranged from 1+ to 2+ (Table 4). To study the connection between amyloid load and transmissibility, we tested AEF-activity of monocytes isolated from mice injected with regular AEF and AgNO3 and sacrificed at different intervals. Two minutes was the shortest studied time point and this was expected to be sufficient to ensure that AEF has been distributed throughout the body (group K1). Six hours (group K2) were expected to be sufficient for AEF to be phagocytosed by monocytes present in circulation. However, we did not observe any amyloid deposits in mice injected with monocytes isolated from K1 and K2 (groups L1 and L2, respectively), Table 5. In mice sacrificed 48 hrs after AEF and AgNO3 injection (group K3) it was possible to detect traces (1+) of amyloid in 3 out of 3 mice, but monocytes isolated from these mice did not reveal any AEF-activity (group L3). The seeding effect was first observed in mice from group L4 that received monocytes isolated from mice sacrificed 7 days after the AEF and AgNO3 injection, group K4. Amyloid was detected in 5 out of 9 mice (56%) (Table 5).


AA-amyloidosis can be transferred by peripheral blood monocytes.

Sponarova J, Nyström SN, Westermark GT - PLoS ONE (2008)

Spleen amyloid deposits stained with Congo red.(A) The amyloid appears pink and is localized to the perifollicular zone. (B) The identical area exhibits green birefringence in polarized light. Amyloid is indicated by arrows.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553266&req=5

pone-0003308-g001: Spleen amyloid deposits stained with Congo red.(A) The amyloid appears pink and is localized to the perifollicular zone. (B) The identical area exhibits green birefringence in polarized light. Amyloid is indicated by arrows.
Mentions: The study continued with analysis of the possibility that peripheral blood monocytes carry amyloid seeds. Profound amounts of amyloid developed in spleen of group G mice after given AEF and 5 weekly AgNO3 injections. Isolated and sonicated peripheral blood monocytes from group G mice were re-injected into new mice (H1-9). Inflammatory stimuli were given to mice in the groups H1-8. These groups varied in size and contained 5–8 animals (Table 2). After Congo red staining, amyloid deposits were detected in 19/48 (40%) of the recipient mice. The amyloid was present in the perifollicular area of the white pulp, and ranged from traces up to moderate amount (1+ to 3+) (Figure 1). The percentage of affected animals differed between groups and in group H2 all mice developed amyloid while this was absent in mice from group H5 and H7 (Table 3). The five animals in group H9 received monocytes isolated from G9 without the concomitant inflammatory stimuli (group H9), and no amyloid developed. Peripheral blood monocytes were also isolated from healthy animals and after sonication injected into nine mice (H10) which received the concomitant inflammatory stimuli. Also in these mice amyloid was absent (Table 2). To validate this phenomenon, peripheral blood monocytes were isolated from the five mice of group H2 that developed AA-amyloid deposits triggered by sonicated peripheral blood monocytes and AgNO3 injections. The isolated monocytes were after sonication reinjected into new groups of healthy mice (groups J1–J5) and AgNO3 was administered as before. Indeed, after 16 days amyloid was present in 80% (12/15) of the animals in group J 1–5. The degree of amyloid ranged from 1+ to 2+ (Table 4). To study the connection between amyloid load and transmissibility, we tested AEF-activity of monocytes isolated from mice injected with regular AEF and AgNO3 and sacrificed at different intervals. Two minutes was the shortest studied time point and this was expected to be sufficient to ensure that AEF has been distributed throughout the body (group K1). Six hours (group K2) were expected to be sufficient for AEF to be phagocytosed by monocytes present in circulation. However, we did not observe any amyloid deposits in mice injected with monocytes isolated from K1 and K2 (groups L1 and L2, respectively), Table 5. In mice sacrificed 48 hrs after AEF and AgNO3 injection (group K3) it was possible to detect traces (1+) of amyloid in 3 out of 3 mice, but monocytes isolated from these mice did not reveal any AEF-activity (group L3). The seeding effect was first observed in mice from group L4 that received monocytes isolated from mice sacrificed 7 days after the AEF and AgNO3 injection, group K4. Amyloid was detected in 5 out of 9 mice (56%) (Table 5).

Bottom Line: The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not be expressed by the monocytes.Plasma recovered from mice with AA amyloidosis lacked seeding capacity.Human AA-amyloidosis resembles the murine form and every individual is expected to be exposed to conditions that initiate production of the acute-phase reactant.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

ABSTRACT
Spongiform encephalopathies have been reported to be transmitted by blood transfusion even prior to the clinical onset. Experimental AA-amyloidosis shows similarities with prion disease and amyloid-containing organ-extracts can prime a recipient for the disease. In this systemic form of amyloidosis N-terminal fragments of the acute-phase reactant apolipoprotein serum amyloid A are the main amyloid protein. Initial amyloid deposits appear in the perifollicular region of the spleen, followed by deposits in the liver. We used the established murine model and induced AA-amyloidosis in NMRI mice by intravenous injections of purified amyloid fibrils ('amyloid enhancing factor') combined with inflammatory challenge (silver nitrate subcutaneously). Blood plasma and peripheral blood monocytes were isolated, sonicated and re-injected into new recipients followed by an inflammatory challenge during a three week period. When the animals were sacrificed presence of amyloid was analyzed in spleen sections after Congo red staining. Our result shows that some of the peripheral blood monocytes, isolated from animals with detectable amyloid, contained amyloid-seed that primed for AA-amyloid. The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not be expressed by the monocytes. Plasma recovered from mice with AA amyloidosis lacked seeding capacity. Amyloid enhancing activity can reside in monocytes recovered from mice with AA-amyloidosis and in a prion-like way trigger amyloid formation in conjunction with an inflammatory disorder. Human AA-amyloidosis resembles the murine form and every individual is expected to be exposed to conditions that initiate production of the acute-phase reactant. The monocyte-transfer mechanism should be eligible for the human disease and we point out blood transfusion as a putative route for transfer of amyloidosis.

Show MeSH
Related in: MedlinePlus