Packed Red Blood Cell Transfusion Modulates Myeloid Dendritic Cell Activation and Inflammatory Response In Vitro

2018 ◽  
Vol 38 (3) ◽  
pp. 111-121 ◽  
Author(s):  
Katrina K. Ki ◽  
Helen M. Faddy ◽  
Robert L. Flower ◽  
Melinda M. Dean
Keyword(s):  
Dendritic Cell ◽  
Inflammatory Response ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Cell Activation ◽  
Red Blood Cell Transfusion ◽  
Myeloid Dendritic Cell ◽  
Dendritic Cell Activation

scholarly journals Impact of Red Blood Cell Transfusion on Platelet Aggregation and Inflammatory Response in Anemic Coronary and Noncoronary Patients

2014 ◽  
Vol 63 (13) ◽  
pp. 1289-1296 ◽  
Author(s):  
Johanne Silvain ◽  
Jérémie Abtan ◽  
Mathieu Kerneis ◽  
Réjane Martin ◽  
Jonathan Finzi ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Inflammatory Response ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Red Blood Cell Transfusion

Hemoglobinuria and Mechanical Hemolysis Associated with Red Blood Cell Transfusion in Pediatric Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3429-3429 ◽  
Author(s):  
Janet McNaughton ◽  
Jonathan Hughes ◽  
Jennifer C. Andrews ◽  
Tracy I. George ◽  
Cassandra Bergero ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Conflicts Of Interest ◽  
Infusion Pump ◽  
Red Blood Cell Transfusion ◽  
Treatment Center ◽  
Outpatient Unit ◽  
Time Period ◽  
Additive Solution

Abstract Abstract 3429 Introduction: Mechanical hemolysis is a non-immune mediated destruction of red blood cells that can be associated with blood transfusion. Various etiologies include the use of blood warmers, small bore needles or high infusion rates. We report the investigation of hemoglobinuria cases observed post-packed red blood cell (PRBC) transfusion with subsequent changes in management. Case report: Over a time period of 2 months, 6 events of hemoglobinuria and hemolysis were reported in 5 patients in the pediatric hematology/oncology treatment center. Each child presented with abnormally tea-colored urine following PRBC transfusion. Transfusion reaction workup included a direct antiglobulin test (DAT), urinalysis (UA), serum haptoglobin (H), lactate dehydrogenase (LDH), and total bilirubin (T-B). All patients had a negative or unchanged DAT, negative RBC antibody screen, decreased H, increased T-B, and increased LDH (4 out of 6), suggestive of intravascular hemolysis (Table). In spite of hemolysis, hemoglobin (Hgb)/hematocrit(Hct) increased normally. Multiple factors were investigated to determine a cause: collection and processing of blood units; handling of blood at the transfusion service; and blood administration by nursing staff. The only significant change identified was the implementation of a new infusion pump (pump A) replacing a model that was phased out. A hospital-wide retrospective review of urinalysis (UA) was performed over a one month time period, along with prospective UA surveillance in the outpatient unit. Results: In the 6 cases, a total of 10 irradiated PRBC units (7 with citrate phosphate dextrose buffer (CPDA1, HCT 65–80%) and 3 with additive solution (AS-5, HCT 55–65%)) were transfused. Although Pump A had been validated by the manufacturer with non-irradiated additive solution units, an in vitro study with irradiated CPDA1 RBC units was performed to compare pump A with an alternative pump B. Samples were taken after infusion using the pumps only (no needle or catheter) and dripped directly into the test tube for measurement of free hemoglobin (FHb). Irradiated CPDA1 units infused at a low rate (50ml/hr) showed an increase in FHb level at 1998mg/dL with pump A versus 496 mg/dL with pump B. Non-irradiated AS-5 units tested as controls resulted in a FHb level at 246mg/dL with pump A versus 117mg/dL with pump B. CPDA1 units were subsequently replaced with AS-5 units for transfusion. Finally, pump A was replaced by pump B in the outpatient hematology oncology unit. In vitro studies are still ongoing to determine if irradiation of the PRBC may also play a role in the mechanical hemolysis observed with pump A. One month retrospective UA review found no association between patients with hemoglobinuria and RBC transfusion. The UA prospective surveillance performed in the outpatient unit revealed that 7 of 26 patients had trace hemoglobinuria. Each one had a confounding factor (chronic hemolysis) for hemoglobinuria. Conclusion: Preliminary investigation determined that the infusion of highly concentrated irradiated RBC (CDPA1) using a specific commercial pump was associated with mechanical hemolysis. The change to less concentrated RBC units through an alternative pump has been to date, an effective corrective action. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Safety of Red Blood Cell Transfusion Using Small Central Lines in Neonates: An in vitro Non-inferiority Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Flavia Rosa-Mangeret ◽  
Sophie Waldvogel-Abramowski ◽  
Riccardo E. Pfister ◽  
Olivier Baud ◽  
Sébastien Fau
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Transfusion Practice ◽  
Red Blood Cell Transfusion ◽  
Central Lines ◽  
Catheter Occlusion ◽  
Prospective Assessment ◽  
Secondary Endpoints ◽  
Central Catheters

Aim: This study aimed to investigate the safety of transfusing red blood cell concentrates (RBCCs) through small [24 gauge (24G)] and extra-small [28 gauge [28G)] peripherally inserted central catheters (PICCs), according to guidelines of transfusion practice in Switzerland.Methods: We performed a non-inferiority in vitro study to assess the safety of transfusing RBCC for 4 h at a 4 ml/h speed through 24G silicone and 28G polyurethane PICC lines, compared with a peripheral 24G short catheter. The primary endpoint was hemolysis percentage. Secondary endpoints were catheter occlusion, inline pressure, and potassium and lactate values.Results: For the primary outcome, hemolysis values were not statistically different among catheter groups (0.06% variation, p = 0.95) or over time (2.75% variation, p = 0.72). The highest hemolysis values in both 24G and 28G PICCs were below the non-inferiority predefined margin. We did not observe catheter occlusion. Inline pressure varied between catheters but followed the same pattern of rapid increase followed by stabilization. Potassium and lactate measurements were not statistically different among tested catheters (0.139% variation, p = 0.98 for potassium and 0.062%, p = 0.96 for lactates).Conclusions: This study shows that RBCC transfusion performed in vitro through 24G silicone and 28G polyurethane PICC lines is feasible without detectable hemolysis or pressure concerns. Also, it adds that, concerning hemolysis, transfusion of RBCC in small and extra-small PICC lines is non-inferior to peripheral short 24G catheters. Clinical prospective assessment in preterm infants is needed to confirm these data further.

scholarly journals Simultaneous Blocking of Human Toll-Like Receptors 2 and 4 Suppresses Myeloid Dendritic Cell Activation Induced by Mycobacterium bovis Bacillus Calmette-Guérin Peptidoglycan

2003 ◽  
Vol 71 (8) ◽  
pp. 4238-4249 ◽  
Author(s):  
Junji Uehori ◽  
Misako Matsumoto ◽  
Shoutaro Tsuji ◽  
Takashi Akazawa ◽  
Osamu Takeuchi ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Mycobacterium Bovis ◽  
Cell Activation ◽  
Hek293 Cells ◽  
Myeloid Dendritic Cell ◽  
Dendritic Cell Activation ◽  
Double Knockout ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Dc Maturation

ABSTRACT The Mycobacterium bovis bacillus Calmette-Guérin (BCG) cell wall skeleton (CWS) consists of mycolic acids, arabinogalactan, and peptidoglycan (PGN) and activates Toll-like receptor 2 (TLR2) and TLR4. Here we investigated the ability of the essential portion of highly purified BCG CWS to support the TLR agonist function by using the following criteria: myeloid dendritic cell (DC) maturation, i.e., tumor necrosis factor alpha (TNF-α) production and CD83/CD86 up-regulation. The purified PGN region was sufficient to activate TLR2 and TLR4 in mouse DCs and macrophages; in TLR2 and TLR4 double-knockout cells the BCG PGN-mediated TNF-α production ability was completely impaired. Likewise, stimulation with BCG CWS of HEK293 cells expressing either human TLR2 or TLR4, MD-2, and CD14 resulted in NF-κB activation as determined by a reporter assay. Notably, specific blockers of extracellular human TLR2 (an original cocktail of monoclonal antibodies TLR2.45 and TH2.1) and TLR4 (E5531) inhibited BCG CWS-mediated NF-κB activation by 80%. Using this human TLR blocking system, we tested whether human myeloid DC maturation was TLR2 and TLR4 dependent. BCG PGN-mediated DC maturation was blocked by 70% by suppression of both TLR2 and TLR4 and by 30 to 40% by suppression of either of these TLRs. Similar but less profound suppression of BCG CWS-mediated DC maturation was observed. Hence, the presence of BCG PGN is a minimal requirement for activation of both TLR2 and TLR4 in human DCs, unlike the presence of PGNs of gram-positive bacteria, which activate only TLR2. Unexpectedly, however, BCG PGN, unlike BCG CWS, barely activated NF-κB in HEK293 cells coexpressing TLR2 plus TLR1, TLR2 plus TLR4, TLR2 plus TLR6, or TLR2 plus TLR10, suggesting that PGN receptors other than TLR2 and TLR4 present on human DCs but not on HEK293 cells are involved in TLR signaling for DC activation.

scholarly journals Anti–IL6-receptor-alpha (tocilizumab) does not inhibit human monocyte-derived dendritic cell maturation or alloreactive T-cell responses

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5340-5343 ◽  
Author(s):  
Brian C. Betts ◽  
Erin T. St Angelo ◽  
Michael Kennedy ◽  
James W. Young
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Activation ◽  
Human Monocyte ◽  
T Cell Proliferation ◽  
Dendritic Cell Activation ◽  
Alloreactive T Cell

Abstract Significant comorbidites and lethality complicate GVHD and its treatment. Targeting the cytokine milieu may improve GVHD control; and IL6 is an attractive candidate, given its role in dendritic cell activation and T-cell differentiation. Tocilizumab is a humanized mAb to IL6-receptor-α (IL6R-α), which is Food and Drug Administration–approved for treatment of rheumatoid arthritis. Mouse transplant models have demonstrated that IL6 blockade also improves GVHD scores and survival. Definitive immunologic effects of IL6 inhibition have not emerged given inconsistent alterations in regulatory T cells (Tregs) and suppression of T-cell proliferation. Despite on-target suppression of IL6R-α signaling in human monocyte-derived dendritic cells (moDCs) and T cells, our data show no effect on moDC maturation/activation, alloreactive T-cell proliferation, Treg expansion, or allogeneic Th1/Th17 responses in vitro. These findings merit attention in any clinical trials of tocilizumab for GVHD prevention or treatment and provide a rationale for evaluating more specific inhibitors of downstream JAK2/STAT3 signaling as well.

scholarly journals CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Enhao Li ◽  
Xiaobao Yang ◽  
Yuzhang Du ◽  
Guanzheng Wang ◽  
David W. Chan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dendritic Cell ◽  
Cell Activation ◽  
Suppressor Cells ◽  
The Cancer Genome Atlas ◽  
Dendritic Cell Activation ◽  
Antitumor Effects ◽  
Activation Markers

Accumulating evidence suggests that tumor-infiltrating immune cells (TICs) in the tumor microenvironment (TME) serve as promising therapeutic targets. CXCL8 (IL-8) may also be a potential therapeutic target in cancer. CXCL8 is a potent chemotactic factor for neutrophils, myeloid-derived suppressor cells (MDSCs) and monocytes, which are considered immunosuppressive components in cancer-bearing hosts. Here, we identified the TME-related gene CXCL8 in a high-ImmuneScore population that contributed to better survival in colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database. An integrated gene profile and functional analysis of TIC proportions revealed that the dendritic cell (DC) activation markers CD80, CD83, and CD86 were positively correlated with CXCL8 expression, suggesting that CXCL8 may be functional as antitumor immune response status in the TME. The gene signature was further validated in independent GSE14333 and GSE38832 cohorts from the Gene Expression Omnibus (GEO). To test the differential contributions of immune and tumor components to progression, three CRC cell lines, CT26, MC38 and HCT116, were used. In vitro results suggested no significant growth or survival changes following treatment with an inhibitor of the CXCL8 receptor (CXCR1/2) such as reparixin or danirixin. In vivo treatment with danirixin (antagonists of CXCR2) promoted tumor progression in animal models established with CT26 cells. CXCR2 antagonism may function via an immune component, with CXCR2 antagonist treatment in mice resulting in reduced activated DCs and correlating with decreased Interferon gamma (IFN-γ) or Granzyme B expressed CD8+ T cells. Furthermore, CXCL8 induced DC migration in transwell migration assays. Taken together, our data suggested that targeting the CXCL8-CXCR2 axis might impede DC activation or recruitment, and this axis could be considered a favorable factor rather than a target for critical antitumor effects on CRC.

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