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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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(A) Flow cytometry analysis of isolated and cultured fraction of peripheral blood monocytic cells (PBMC). The measurements were performed using forward scatter versus side scatter and 10,000 events were recorded. The marked area represents monocytic population and four independent isolations were analyzed. The monocyte population was determined to 64%±15% (mean±SD). Insert shows analysis of PBMC prior to culture. (B) Representative picture of a cell recovered after isolation and culture. Bar 1 uM.
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pone-0003308-g002: (A) Flow cytometry analysis of isolated and cultured fraction of peripheral blood monocytic cells (PBMC). The measurements were performed using forward scatter versus side scatter and 10,000 events were recorded. The marked area represents monocytic population and four independent isolations were analyzed. The monocyte population was determined to 64%±15% (mean±SD). Insert shows analysis of PBMC prior to culture. (B) Representative picture of a cell recovered after isolation and culture. Bar 1 uM.

Mentions: Peripheral blood monocytes were isolated from relatively small volumes of 1 ml blood. With the Ficoll-Paque isolation procedure granulocytes are expected to be excluded from the white blood cells that remain on the top of the gradient. During overnight incubation monocytes are expected to adhere to the plastic support while most of the lymphocytes should remain in the non-adherent fraction. Analysis of cells recovered after rinsing and trypsination revealed an enrichment of monocytes. Comparison of cytometry analysis of cell isolations before and after overnight culture shows an enrichment of cells with monocytes appearance in the latter. The monocyte population of the four different isolations varied (64±15%; mean±SD) (Figure 2A). At high resolution it was shown that the majority of isolated cells were monocytes (Figure 2B).


AA-amyloidosis can be transferred by peripheral blood monocytes.

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

(A) Flow cytometry analysis of isolated and cultured fraction of peripheral blood monocytic cells (PBMC). The measurements were performed using forward scatter versus side scatter and 10,000 events were recorded. The marked area represents monocytic population and four independent isolations were analyzed. The monocyte population was determined to 64%±15% (mean±SD). Insert shows analysis of PBMC prior to culture. (B) Representative picture of a cell recovered after isolation and culture. Bar 1 uM.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003308-g002: (A) Flow cytometry analysis of isolated and cultured fraction of peripheral blood monocytic cells (PBMC). The measurements were performed using forward scatter versus side scatter and 10,000 events were recorded. The marked area represents monocytic population and four independent isolations were analyzed. The monocyte population was determined to 64%±15% (mean±SD). Insert shows analysis of PBMC prior to culture. (B) Representative picture of a cell recovered after isolation and culture. Bar 1 uM.
Mentions: Peripheral blood monocytes were isolated from relatively small volumes of 1 ml blood. With the Ficoll-Paque isolation procedure granulocytes are expected to be excluded from the white blood cells that remain on the top of the gradient. During overnight incubation monocytes are expected to adhere to the plastic support while most of the lymphocytes should remain in the non-adherent fraction. Analysis of cells recovered after rinsing and trypsination revealed an enrichment of monocytes. Comparison of cytometry analysis of cell isolations before and after overnight culture shows an enrichment of cells with monocytes appearance in the latter. The monocyte population of the four different isolations varied (64±15%; mean±SD) (Figure 2A). At high resolution it was shown that the majority of isolated cells were monocytes (Figure 2B).

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