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Stored red blood cells selectively activate human neutrophils to release IL-8 and secretory PLA2
G Zallen1, E E Moore, D J Ciesla
1Department of Surgery, Denver Health Medical Center and University of Colorado Health Sciences Center, 80204, USA.
Abstract:
Packed red blood cell (PRBC) transfusion has been invoked previously with immunosuppression and increased infections, but it has now been demonstrated that stored PRBCs (>14 days) can prime PMNs and provoke multiple organ failure. Recently, the role of PMNs in the genesis of MOF has been extended to their release of inflammatory cytokines, notably IL-1, IL-8, TNFalpha, and secretory phospholipase A2 (sPLA2). We hypothesize that stored PRBCs can act as a second event via stimulating the release of inflammatory cytokines from PMNs. Isolated human PMNs were incubated for 24 h in RPMI with either 20% fresh plasma or plasma from 42 day old PRBC (day of outdate) and release of IL-8, IL-1beta, TNFalpha, and sPLA2 were measured. Plasma from stored PRBCs contained small amounts of IL-8, sPLA2, and TNFalpha (102.1 +/-5.6 pg/ml, 87.6+/-6.0 pg/ml and 9.7+/-.7 pg/ml). Levels of IL-1beta were below detection (<1 pg/ml). Day 42 PRBC plasma stimulated significant PMN release of both IL-8 and sPLA2 as compared to both control and day 0 plasma (*P < .05), but PRBC plasma did not stimulate PMN release of either IL-1beta or TNFalpha. Transfused blood is emerging as an inflammatory agent that is capable of producing PMN priming. In this study we have demonstrated that PRBC plasma selectively activates PMNs to release both IL-8 and sPLA2. Thus, transfusion of PRBCs may represent a preventable inflammatory insult via modification of both blood banking and transfusion practices.
Insights
Stored packed red blood cells (PRBCs) can activate neutrophils (PMNs), leading to the release of inflammatory cytokines IL-8 and sPLA2. This suggests PRBC transfusions may be a preventable inflammatory trigger.
Area of Science:
- Immunology
- Hematology
- Critical Care Medicine
Background:
- Packed red blood cell (PRBC) transfusions have been linked to immunosuppression and infections.
- Stored PRBCs (>14 days) may prime neutrophils (PMNs) and contribute to multiple organ failure (MOF).
- Neutrophil-derived inflammatory cytokines, including IL-1, IL-8, TNFalpha, and secretory phospholipase A2 (sPLA2), are implicated in MOF.
Purpose of the Study:
- To investigate the hypothesis that stored PRBCs act as a secondary inflammatory event by stimulating cytokine release from PMNs.
- To determine if plasma from stored PRBCs can induce the release of inflammatory cytokines from isolated human PMNs.
Main Methods:
- Isolated human PMNs were incubated with either fresh plasma or plasma from 42-day-old PRBCs.
- The release of IL-8, IL-1beta, TNFalpha, and sPLA2 from PMNs was measured.
- Plasma from stored PRBCs was analyzed for baseline cytokine levels.
Main Results:
- Plasma from stored PRBCs contained detectable levels of IL-8, sPLA2, and TNFalpha.
- Stored PRBC plasma significantly stimulated PMN release of IL-8 and sPLA2 compared to control and fresh plasma.
- Stored PRBC plasma did not stimulate the release of IL-1beta or TNFalpha from PMNs.
Conclusions:
- Transfusion of stored PRBCs can act as an inflammatory agent, priming PMNs.
- PRBC plasma selectively activates PMNs to release IL-8 and sPLA2.
- Modifying blood banking and transfusion practices could mitigate the inflammatory insult associated with PRBC transfusions.