Limits...
In vitro and in vivo characterization of ultraviolet light C-irradiated human platelets in a 2 event mouse model of transfusion.

Zhi L, Chi X, Vostal JG - PLoS ONE (2013)

Bottom Line: UVC-based technology differs from UVA or UVB-based technologies in that it uses a specific wavelength at 254 nm without the addition of any photosensitizers.Previously, it was reported that UVC irradiation induces platelet aggregation and activation.Unlike UVB-platelets, UVC-platelets did not lead to lung injury or induce MIP-2 release.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular Hematology, Division of Hematology, OBRR, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.

ABSTRACT
UV-based pathogen reduction technologies have been developed in recent years to inactivate pathogens and contaminating leukocytes in platelet transfusion products in order to prevent transfusion-transmitted infections and alloimmunization. UVC-based technology differs from UVA or UVB-based technologies in that it uses a specific wavelength at 254 nm without the addition of any photosensitizers. Previously, it was reported that UVC irradiation induces platelet aggregation and activation. To understand if UVC-induced changes of platelet quality correlate with potential adverse events when these platelets are transfused into animals, we used a 2-event SCID mouse model in which the predisposing event was LPS treatment and the second event was infusion of UVC-irradiated platelets. We analyzed lung platelet accumulation, protein content in bronchoalveolar lavage fluid as an indication of lung injury, and macrophage inflammatory protein-2 (MIP-2) release in mice received UVC-irradiated or untreated control platelets. Our results showed UVC-irradiated platelets accumulated in lungs of the mice in a dose-dependent manner. High-doses of UVC-irradiated platelets were sequestered in the lungs to a similar level as we previously reported for UVB-irradiated platelets. Unlike UVB-platelets, UVC-platelets did not lead to lung injury or induce MIP-2 release. This could potentially be explained by our observation that although UVC treatment activated platelet surface αIIbβ3, it failed to activate platelet cells. It also suggests lung platelet accumulation and subsequent lung damage are due to different and separate mechanisms which require further investigation.

Show MeSH

Related in: MedlinePlus

UVC-irradiated HPs showed reduced in vivo recovery in circulation of SCID mice.Approximately 1 x 109 untreated (open circle) or UVC-irradiated HPs at a dose of 0.2 J/cm2 (filled square) were infused into SCID mice. Blood sampling was subsequently performed at indicated time points and the presence of human platelets in circulation positive for anti-human CD41a staining was detected by flow cytometry. Mean ± SE, n=5.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3815158&req=5

pone-0079869-g003: UVC-irradiated HPs showed reduced in vivo recovery in circulation of SCID mice.Approximately 1 x 109 untreated (open circle) or UVC-irradiated HPs at a dose of 0.2 J/cm2 (filled square) were infused into SCID mice. Blood sampling was subsequently performed at indicated time points and the presence of human platelets in circulation positive for anti-human CD41a staining was detected by flow cytometry. Mean ± SE, n=5.

Mentions: To assess the impact of UVC irradiation on platelets in vivo, we compared the survival and recovery of human platelets exposed to either a UVC dose of 0.2 J/cm2 or untreated control platelets in SCID mice circulation . Approximately 1 x 109 human platelets were transfused into each animal. Using the percentage of cells positive for the specific human CD41 antibody staining in the platelet acquisition gate of control platelets at 5 minutes after platelet infusion as 100 % recovery, the recovery of UVC and control platelets was evaluated at 5 and 20 minutes and at 2, 4, 6, and 24 hours after platelet infusion (Figure 3). We found that the recovery of UVC platelets in circulation at 5 minutes after infusion was 39.1 % lower than that of control platelets (60.9 ± 20.5% vs 100 ± 7.4%). The presence of UVC-platelets in circulation was quickly reduced within 20 minutes, resulting in 78.6 % lower recovery than control platelets (28.4 ± 3.6% vs 107 ± 31.1%). By 2 hours after infusion, the level of UVC platelets in circulation increased and the difference in recovery between UVC and control platelets persisted at about 35 % at 2, 4 and 6 hours (50.5 ± 7% vs 88.2 ± 7.9%, 36.2 ± 6.8% vs 72.7 ± 3%, and 15.6 ± 0.3% vs 48.9 ± 6.6%, respectively). By 24 hours after infusion, the recovery of both UVC and control platelets approached zero. The approximate t1/2 of human platelets in mouse circulation estimated graphically and defined as the time to reach 50 % recovery, was about 2 hours for UVC platelets and 6 hours for control platelets in SCID mice.


In vitro and in vivo characterization of ultraviolet light C-irradiated human platelets in a 2 event mouse model of transfusion.

Zhi L, Chi X, Vostal JG - PLoS ONE (2013)

UVC-irradiated HPs showed reduced in vivo recovery in circulation of SCID mice.Approximately 1 x 109 untreated (open circle) or UVC-irradiated HPs at a dose of 0.2 J/cm2 (filled square) were infused into SCID mice. Blood sampling was subsequently performed at indicated time points and the presence of human platelets in circulation positive for anti-human CD41a staining was detected by flow cytometry. Mean ± SE, n=5.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815158&req=5

pone-0079869-g003: UVC-irradiated HPs showed reduced in vivo recovery in circulation of SCID mice.Approximately 1 x 109 untreated (open circle) or UVC-irradiated HPs at a dose of 0.2 J/cm2 (filled square) were infused into SCID mice. Blood sampling was subsequently performed at indicated time points and the presence of human platelets in circulation positive for anti-human CD41a staining was detected by flow cytometry. Mean ± SE, n=5.
Mentions: To assess the impact of UVC irradiation on platelets in vivo, we compared the survival and recovery of human platelets exposed to either a UVC dose of 0.2 J/cm2 or untreated control platelets in SCID mice circulation . Approximately 1 x 109 human platelets were transfused into each animal. Using the percentage of cells positive for the specific human CD41 antibody staining in the platelet acquisition gate of control platelets at 5 minutes after platelet infusion as 100 % recovery, the recovery of UVC and control platelets was evaluated at 5 and 20 minutes and at 2, 4, 6, and 24 hours after platelet infusion (Figure 3). We found that the recovery of UVC platelets in circulation at 5 minutes after infusion was 39.1 % lower than that of control platelets (60.9 ± 20.5% vs 100 ± 7.4%). The presence of UVC-platelets in circulation was quickly reduced within 20 minutes, resulting in 78.6 % lower recovery than control platelets (28.4 ± 3.6% vs 107 ± 31.1%). By 2 hours after infusion, the level of UVC platelets in circulation increased and the difference in recovery between UVC and control platelets persisted at about 35 % at 2, 4 and 6 hours (50.5 ± 7% vs 88.2 ± 7.9%, 36.2 ± 6.8% vs 72.7 ± 3%, and 15.6 ± 0.3% vs 48.9 ± 6.6%, respectively). By 24 hours after infusion, the recovery of both UVC and control platelets approached zero. The approximate t1/2 of human platelets in mouse circulation estimated graphically and defined as the time to reach 50 % recovery, was about 2 hours for UVC platelets and 6 hours for control platelets in SCID mice.

Bottom Line: UVC-based technology differs from UVA or UVB-based technologies in that it uses a specific wavelength at 254 nm without the addition of any photosensitizers.Previously, it was reported that UVC irradiation induces platelet aggregation and activation.Unlike UVB-platelets, UVC-platelets did not lead to lung injury or induce MIP-2 release.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular Hematology, Division of Hematology, OBRR, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.

ABSTRACT
UV-based pathogen reduction technologies have been developed in recent years to inactivate pathogens and contaminating leukocytes in platelet transfusion products in order to prevent transfusion-transmitted infections and alloimmunization. UVC-based technology differs from UVA or UVB-based technologies in that it uses a specific wavelength at 254 nm without the addition of any photosensitizers. Previously, it was reported that UVC irradiation induces platelet aggregation and activation. To understand if UVC-induced changes of platelet quality correlate with potential adverse events when these platelets are transfused into animals, we used a 2-event SCID mouse model in which the predisposing event was LPS treatment and the second event was infusion of UVC-irradiated platelets. We analyzed lung platelet accumulation, protein content in bronchoalveolar lavage fluid as an indication of lung injury, and macrophage inflammatory protein-2 (MIP-2) release in mice received UVC-irradiated or untreated control platelets. Our results showed UVC-irradiated platelets accumulated in lungs of the mice in a dose-dependent manner. High-doses of UVC-irradiated platelets were sequestered in the lungs to a similar level as we previously reported for UVB-irradiated platelets. Unlike UVB-platelets, UVC-platelets did not lead to lung injury or induce MIP-2 release. This could potentially be explained by our observation that although UVC treatment activated platelet surface αIIbβ3, it failed to activate platelet cells. It also suggests lung platelet accumulation and subsequent lung damage are due to different and separate mechanisms which require further investigation.

Show MeSH
Related in: MedlinePlus