Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neu...Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection.However,recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions.Accordingly,neutrophils are emerging as highly versatile cells that are able to acquire different,often opposite,functional capacities depending on the microenvironment and their differentiation status.Herein,we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT,from the hematopoietic stem cell(HSC)mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion.We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versushost disease(GVHD)prophylaxis.Finally,the potential involvement of neutrophils in alloHSCT-related complications,such as transplant-associated thrombotic microangiopathy(TA-TMA),acute and chronic GVHD,and cytomegalovirus(CMV)reactivation,is also discussed.Based on the data reviewed herein,the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role.However,much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.展开更多
Objective： Low-density granulocytes （LDGs） can form neutrophil extracellular traps （NETs） spontaneously and excessively. When peripheral blood mononuclear calls （PBMCs） are used for studying T lymphocytes, LDGs...Objective： Low-density granulocytes （LDGs） can form neutrophil extracellular traps （NETs） spontaneously and excessively. When peripheral blood mononuclear calls （PBMCs） are used for studying T lymphocytes, LDGs contained in the PBMCs may decrease the threshold of activating T lymphocytes by forming NETs. This study focused on the profiles of LDGs in common autoimmune diseases and methods for removing LDGs from PBMCs. Methods： The percentages of LDGs in PBMCs from 55 patients with dermatomyositis （DM）, 15 with polymyositis （PM）, 42 with rheumatoid arthritis （RA）, 25 with systemic lupus erythematosus （SLE）, and 19 healthy controls were determined by flow cytometry. Three methods of removing LDGs were explored and compared. After removal, PBMCs from six patients with positive T-SPOT.TB were tested again to find out if LDGs contained in the PBMCs could influence T lymphocyte reactions. Results： Significantly higher LDG percentages were found in PBMCs from patients with DM （（8.41±10.87）%, P〈0.0001 ）, PM （（8.41±10.39）%, P〈0.0001 ）, RA （（4.05±6.97）%, P=0.0249）, and SLE （（7.53±11.52）%, P=0.0006）, compared with the controls （（1.28±0.73）%）. The T-SPOT.TB values significantly decreased after LDGs were removed. Increasing relative centrifugal force （RCF） within a limited range can decrease the LDG percentage from an initial high level, but not markedly increase the LDG clearance rate. Compared with the whole blood sediment method, the PBMC adherence method can significantly remove LDGs yet scarcely influence the T lymphocyte percentage in PBMCs. Conclusions： The LDG percentage in PBMCs is significantly increased in patients with S/E, DM, PM, and RA. The influence of LDGs on T lymphocytes cannot be ignored in PBMC cultures. The adherence method is a simple and easy-to-use method for removing LDGs and purifying T lymphocytes from PBMCs.展开更多
基金supported by grants from Associazione Italiana per la Ricerca sul Cancro(AIRC,IG-20339)Ministero delllstruzione,deirUniversitci e della Ricerca(MIUR-PRIN 20177J4E75_004)Fondazione Cariverona to MAC。
文摘Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow failures.The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection.However,recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions.Accordingly,neutrophils are emerging as highly versatile cells that are able to acquire different,often opposite,functional capacities depending on the microenvironment and their differentiation status.Herein,we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT,from the hematopoietic stem cell(HSC)mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion.We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versushost disease(GVHD)prophylaxis.Finally,the potential involvement of neutrophils in alloHSCT-related complications,such as transplant-associated thrombotic microangiopathy(TA-TMA),acute and chronic GVHD,and cytomegalovirus(CMV)reactivation,is also discussed.Based on the data reviewed herein,the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role.However,much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.
基金Project supported by the National Natural Science Foundation of China(Nos.81560267 and 81401363)the Natural Science Foundation of Gansu Province(No.1606RJZA213)the Asia Pacific League of Associations for Rheumatology(APLAR) Research Grant 2015
文摘Objective： Low-density granulocytes （LDGs） can form neutrophil extracellular traps （NETs） spontaneously and excessively. When peripheral blood mononuclear calls （PBMCs） are used for studying T lymphocytes, LDGs contained in the PBMCs may decrease the threshold of activating T lymphocytes by forming NETs. This study focused on the profiles of LDGs in common autoimmune diseases and methods for removing LDGs from PBMCs. Methods： The percentages of LDGs in PBMCs from 55 patients with dermatomyositis （DM）, 15 with polymyositis （PM）, 42 with rheumatoid arthritis （RA）, 25 with systemic lupus erythematosus （SLE）, and 19 healthy controls were determined by flow cytometry. Three methods of removing LDGs were explored and compared. After removal, PBMCs from six patients with positive T-SPOT.TB were tested again to find out if LDGs contained in the PBMCs could influence T lymphocyte reactions. Results： Significantly higher LDG percentages were found in PBMCs from patients with DM （（8.41±10.87）%, P〈0.0001 ）, PM （（8.41±10.39）%, P〈0.0001 ）, RA （（4.05±6.97）%, P=0.0249）, and SLE （（7.53±11.52）%, P=0.0006）, compared with the controls （（1.28±0.73）%）. The T-SPOT.TB values significantly decreased after LDGs were removed. Increasing relative centrifugal force （RCF） within a limited range can decrease the LDG percentage from an initial high level, but not markedly increase the LDG clearance rate. Compared with the whole blood sediment method, the PBMC adherence method can significantly remove LDGs yet scarcely influence the T lymphocyte percentage in PBMCs. Conclusions： The LDG percentage in PBMCs is significantly increased in patients with S/E, DM, PM, and RA. The influence of LDGs on T lymphocytes cannot be ignored in PBMC cultures. The adherence method is a simple and easy-to-use method for removing LDGs and purifying T lymphocytes from PBMCs.
