Platelets as immune-sensing cells

Kapur, Rick; Semple, John W.

doi:10.1182/bloodadvances.2016000067

Cited by 53 publications

(54 citation statements)

References 70 publications

(53 reference statements)

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“…While platelets are best known for their role in haemostasis, they are also involved in innate and adaptive immunity (Semple et al, 2011). Platelets and their secreted molecules can interact with multiple cell types (antigen-presenting cells, T cells, and B cells, among others) (Morrell et al, 2007;Verschoor et al, 2011;Chapman et al, 2012;Kapur et al, 2015;Vajen et al, 2015;Kapur & Semple, 2016;Melki et al, 2017;Zufferey et al, 2017;Koupenova et al, 2018). The impact of innate/adaptive immune changes due to platelet transfusions on HCT outcomes remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA‐matched haematopoietic cell transplant for sickle cell disease

et al. 2019

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Summary The relevance of donor‐specific human leukocyte antigen (HLA) antibodies in HLA‐mismatched haematopoietic cell transplant (HCT) is known, but the importance of HLA antibodies in HLA‐matched HCT is unclear. We hypothesized that HLA antibodies detected before HCT would cause platelet transfusion refractoriness during HCT and investigated this in a multi‐centre study. Pre‐HCT samples from 45 paediatric patients with sickle cell disease (SCD) undergoing HLA‐matched HCT were tested for HLA class I antibodies. The number of platelet transfusions received before day +45 was compared between those with and without antibodies. Thirteen of 45 (29%) patients had a positive HLA class I antibody screen, and these patients received significantly more platelet transfusions than patients without antibodies (median 19 vs. 7·5, P = 0·028). This platelet transfusion association remained significant when controlling for conditioning regimen. Among alloimmunized patients, there was no association between the panel‐reactive antibody and the number of platelet transfusions. Patients with HLA class I antibodies also had a higher incidence of acute graft‐versus‐host disease (GVHD): 6/13 (46%) vs. 3/32 (9%), P = 0·011. Pre‐HCT HLA class I alloimmunization is associated with increased platelet transfusion support and acute GVHD in paediatric HLA‐matched HCT for SCD. Further studies are needed to investigate the pathobiology of this association.

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Section: Discussionmentioning

confidence: 99%

Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA‐matched haematopoietic cell transplant for sickle cell disease

et al. 2019

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“…Beyond their critical role in hemostasis, platelets can regulate inflammation and infection through multiple mechanisms. Platelets may act as sentinels in the circulation, rapidly bind bloodborne pathogens, and activate several mechanisms that control innate resistance to infection (Semple, Italiano and Freedman, 2011;Kapur et al, 2015;Kapur and Semple, 2016). Platelets express major innate immune-related molecules, including Toll-like receptors (TLRs), complement receptors, adhesion molecules, and mediators essential for recruiting neutrophils and monocytes (Kral et al, 2016;Li, Zarbock and Hidalgo, 2017).…”

Section: Introductionmentioning

confidence: 99%

Platelets Promote Macrophage Polarization toward Pro-inflammatory Phenotype and Increase Survival of Septic Mice

et al. 2019

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“…Nevertheless, inflammation remains a major risk factor for TRALI, the syndrome resulting from a surge of activity in inflammatory cells . Whereas for a long time it was believed that platelet function was solely dedicated to thrombosis and hemostasis, it is now accepted by the scientific community that platelets also play a role in immune and inflammatory responses and, perhaps, potentiate the immunopathology of TRALI . It is noteworthy that these issues remain undiscussed by any of the publications in which platelets are immunologically depleted in a TRALI mouse model.…”

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confidence: 99%

Platelet depletion limits the severity but does not prevent the occurrence of experimental transfusion‐related acute lung injury

et al. 2020

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BACKGROUND Transfusion‐related acute lung injury (TRALI) is a severe pulmonary reaction due to blood transfusions. The pathophysiology of this complication is still not widely elucidated by the scientific community, especially regarding the direct role of blood platelets within the cellular mechanism responsible for the development of TRALI. STUDY DESIGN AND METHODS In this study, a mouse model was used to induce the development of antibody‐mediated acute lung injury through injections of lipopolysaccharide and an anti–major histocompatibility complex Class I antibody. BALB/c mice were pretreated with an anti‐GPIbα antibody, which induces platelet depletion, or ML354, a protease receptor 4 pathway inhibitor, 30 minutes before TRALI induction. RESULTS Depletion of platelets before TRALI induction appeared to reduce the severity of TRALI without completely inhibiting its development. Also, inhibition of platelet activation by ML354 did not prevent the onset of TRALI. Finally, the stimuli used for TRALI induction also triggered specific platelet activation upon ex vivo stimulation. CONCLUSIONS This study suggests that blood platelets are not critically required for TRALI induction, although they are to some extent involved in its pathophysiology.

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Platelets as immune-sensing cells

Cited by 53 publications

References 70 publications

Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA‐matched haematopoietic cell transplant for sickle cell disease

Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA‐matched haematopoietic cell transplant for sickle cell disease

Platelets Promote Macrophage Polarization toward Pro-inflammatory Phenotype and Increase Survival of Septic Mice

Platelet depletion limits the severity but does not prevent the occurrence of experimental transfusion‐related acute lung injury

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