The plasma effects during hypoxia and hemorrhagic shock on the interactions between plymorphonuclear neutrophils (PMNs) and cultured pulmonary artery endothelial cells (PAECs) were studied. The plasma samples were obt...The plasma effects during hypoxia and hemorrhagic shock on the interactions between plymorphonuclear neutrophils (PMNs) and cultured pulmonary artery endothelial cells (PAECs) were studied. The plasma samples were obtained from the goats under the following conditions: (1)Normal control plasma was obtained from the goats at sea level to aserve as the control (CP). (2)Hypoxic plasma was obtained after the goats were exposed to a simulated altitude of 4 000 m for 24 h (HP). (3) Hypotensive hypoxic plasma was obtained after the goats were bled to a mean arterial pressure of 5. 5±0. 3 kpa for 1 h under hypoxic condition (HHP). (4) Retransfused hypoxic plasma was obtained when the hypotensive goats were transfused with the shed blood for 4 h under hypoxic condition (RHP). It was found that HP , HHP and RHP especially RHP exerted profound effects on the activities of PMNs and PAECs in a concentration and time dependent manner after the PMNs and PAECs were incubated in the media containing different concentrations of the 4 kinds of plasma for different durations. Low concentration of RHP (less than 12. 5%) significantly increased the activity of PAECs (P<0. 01 vs CP) but its high concentration (more than 12. 5%) markedly decreased their activity (P<0. 01 vs CP, HP and HHP). HP, HHP and RHP increased the activity of PAECs in the early stage of incubation (1 to 3 h) (P<0. 01 vs CP) but decreased it in the late stage (6 to 12 h) (P<0. 01 vs CP). The activity of PMNs was significantly increased after 1 h incubation with HP, HHP and RHP (PM0. 001) and this effect was also concentrationdependent.The effects of RHP was the most potent, HHP the next and HP the least. The deformability of PMNs was significantly decreased (P <0. 001) after they were incubated in RHP for 3 h. The adhesive force of PMNs and PAECs was also significantly increased after 12 h incubation with RHP. These findings suggest that there are substances in the hypoxic plasma to activate or damage the interactions between PMNs and PAECs and the amounts of the substances are further increased in hypotensive hypoxic plasma and retransfused hypoxic plasma and the 'activation-damage'to PMNs and PAECs and the subsequent interactions between PMNs and PAECs play an important role in the pathological changes of hypoxia and hemorrhagic shock.展开更多
The monocellular adhesive ability of polymorphonuclear neutrophils (PMN)to vascular endothelial cells (VEC) was observed with micromanipulation technique when the cells were treated with endotoxin, Anti-CD18 monoclona...The monocellular adhesive ability of polymorphonuclear neutrophils (PMN)to vascular endothelial cells (VEC) was observed with micromanipulation technique when the cells were treated with endotoxin, Anti-CD18 monoclonal antibodies (McAb),anti-endothelial-leucocytic adhesion molecule-l (ELAM-l)McAb and anti-intercellular adhesion molecule-1 (ICAM-1) McAb and the effects of these 3 adhesion molecules on the development of adhesion force between PMNs and VECs were investigated. It was found that CD18 McAb decreased obviously the adhesive ability of PMNs in the whole course of adhesion increasing and the McAbs of ELAM-1 and ICAMI-1 inhibited most of adhesive force of VECs in the 4th and 12th hour of the course respectively.These findings suggest that the main molecular basis of rapid increase of adhesive ability of PMNs is CD18 expression and that of delayed increase of adhesive ability of VECs is ELAM-1 and ICAM-1 expression.展开更多
Neutrophils,the most abundant leukocytes in human blood,are essential fighter immune cells against microbial infection.Based on the finding that neutrophils can either restrict or promote cancer progression,tumor-asso...Neutrophils,the most abundant leukocytes in human blood,are essential fighter immune cells against microbial infection.Based on the finding that neutrophils can either restrict or promote cancer progression,tumor-associated neutrophils(TAN)are classified into anti-tumor N1 and pro-tumor N2 subsets.One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells,in particular,cytotoxic T lymphocytes.Currently,no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells(G/PMN-MDSC).In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy,as established from data obtained with diverse cancer models,therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy.Here,we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories:(1)depletion of existing PMN-MDSCs,(2)blockade of the development of PMNMDSCs,(3)blockade of PMN-MDSC recruitment,(4)inhibition of immunosuppressive function.Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier,neutrophils are outstanding candidate carriers in nanoparticle-based therapies.Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery.In the second part of the review,we have highlighted recent advances in the field of neutrophil-based cancer drug delivery.Overall,we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits.展开更多
文摘The plasma effects during hypoxia and hemorrhagic shock on the interactions between plymorphonuclear neutrophils (PMNs) and cultured pulmonary artery endothelial cells (PAECs) were studied. The plasma samples were obtained from the goats under the following conditions: (1)Normal control plasma was obtained from the goats at sea level to aserve as the control (CP). (2)Hypoxic plasma was obtained after the goats were exposed to a simulated altitude of 4 000 m for 24 h (HP). (3) Hypotensive hypoxic plasma was obtained after the goats were bled to a mean arterial pressure of 5. 5±0. 3 kpa for 1 h under hypoxic condition (HHP). (4) Retransfused hypoxic plasma was obtained when the hypotensive goats were transfused with the shed blood for 4 h under hypoxic condition (RHP). It was found that HP , HHP and RHP especially RHP exerted profound effects on the activities of PMNs and PAECs in a concentration and time dependent manner after the PMNs and PAECs were incubated in the media containing different concentrations of the 4 kinds of plasma for different durations. Low concentration of RHP (less than 12. 5%) significantly increased the activity of PAECs (P<0. 01 vs CP) but its high concentration (more than 12. 5%) markedly decreased their activity (P<0. 01 vs CP, HP and HHP). HP, HHP and RHP increased the activity of PAECs in the early stage of incubation (1 to 3 h) (P<0. 01 vs CP) but decreased it in the late stage (6 to 12 h) (P<0. 01 vs CP). The activity of PMNs was significantly increased after 1 h incubation with HP, HHP and RHP (PM0. 001) and this effect was also concentrationdependent.The effects of RHP was the most potent, HHP the next and HP the least. The deformability of PMNs was significantly decreased (P <0. 001) after they were incubated in RHP for 3 h. The adhesive force of PMNs and PAECs was also significantly increased after 12 h incubation with RHP. These findings suggest that there are substances in the hypoxic plasma to activate or damage the interactions between PMNs and PAECs and the amounts of the substances are further increased in hypotensive hypoxic plasma and retransfused hypoxic plasma and the 'activation-damage'to PMNs and PAECs and the subsequent interactions between PMNs and PAECs play an important role in the pathological changes of hypoxia and hemorrhagic shock.
文摘The monocellular adhesive ability of polymorphonuclear neutrophils (PMN)to vascular endothelial cells (VEC) was observed with micromanipulation technique when the cells were treated with endotoxin, Anti-CD18 monoclonal antibodies (McAb),anti-endothelial-leucocytic adhesion molecule-l (ELAM-l)McAb and anti-intercellular adhesion molecule-1 (ICAM-1) McAb and the effects of these 3 adhesion molecules on the development of adhesion force between PMNs and VECs were investigated. It was found that CD18 McAb decreased obviously the adhesive ability of PMNs in the whole course of adhesion increasing and the McAbs of ELAM-1 and ICAMI-1 inhibited most of adhesive force of VECs in the 4th and 12th hour of the course respectively.These findings suggest that the main molecular basis of rapid increase of adhesive ability of PMNs is CD18 expression and that of delayed increase of adhesive ability of VECs is ELAM-1 and ICAM-1 expression.
基金partly supported by a graduate fellowship from China Scholarship Council(Grant No.201708340071)partly supported by a Career Catalyst Research Grant(Grant No.18548293)from the Susan G.Komen Foundation+1 种基金a Cancer Research Grant from the Mary Kay Foundationa Research Grant from the Elsa U.Pardee Foundation。
文摘Neutrophils,the most abundant leukocytes in human blood,are essential fighter immune cells against microbial infection.Based on the finding that neutrophils can either restrict or promote cancer progression,tumor-associated neutrophils(TAN)are classified into anti-tumor N1 and pro-tumor N2 subsets.One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells,in particular,cytotoxic T lymphocytes.Currently,no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells(G/PMN-MDSC).In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy,as established from data obtained with diverse cancer models,therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy.Here,we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories:(1)depletion of existing PMN-MDSCs,(2)blockade of the development of PMNMDSCs,(3)blockade of PMN-MDSC recruitment,(4)inhibition of immunosuppressive function.Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier,neutrophils are outstanding candidate carriers in nanoparticle-based therapies.Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery.In the second part of the review,we have highlighted recent advances in the field of neutrophil-based cancer drug delivery.Overall,we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits.
