Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Accumulaed evidence has suggested that heparin＇s anti-inflammatory effects are mainly med...Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Accumulaed evidence has suggested that heparin＇s anti-inflammatory effects are mainly mediated by blocking L-or P-selectin-initiated cell adhesion. Recently, we have reported that periodate-oxidized, borohydridereduced heparin （RO-heparln） can inhibit P-selectin-mediated acute inflammation. Here we further examined the effect of RO-heparin on the adhesion of L-selectin-mediated leukocytes to vascular endothelium under flow conditions in vivo and in vitro. The results show that RO-heparin with a low anticoagulant activity can effectively reduce leucocyte roiling on thioglycoUate-induced rat mesenterlc venules and L-selectin-metadiated neutrophil roiling on TNF-α-induced human umbilical vein endothelial cells（HUVECs） under flow conditions. Our findings suggest that the effect of RO-heparin on inflammatory responses is mainly a result of its inhibiting the interaction between P- or L-selectin and its ligands. The findings also suggest that RO-heparin may be useful in preventing inflammation diseases.展开更多
Objective： To compare carotid catheters blooddrawing and tail-cut blooddrawing in traumatizing rats and changing their intemal L-selectin. Methods： Two ways of bloodletting were selected to produce hemorrhagic shock...Objective： To compare carotid catheters blooddrawing and tail-cut blooddrawing in traumatizing rats and changing their intemal L-selectin. Methods： Two ways of bloodletting were selected to produce hemorrhagic shock models. Monoclonal antibody sign and flow cytometer were used to test neutrophil L-selectin dynamic expression in rats. Results： No remarkable differences were shown among different time points in neutrophil L-selectin expressing amount （ average fluorescence index） （ P 〉 0.05）. Compared with the normal control group, all cell surface expressions in empirical control group increased. Cell surface expressions reached the summit at 3 hours and kept the high level at 4-5 hours. A progressive increase of the mRNA expression peaked at 5 hours; the expressions in both groups of carotid catheters blooddrawing increased compared with normal control group, and remained stable after 3 hours compared with the Tail-cut Blooddrawing Group. Conclusion： L-sclectin expressions changed little in tail-cut blooddrawing rats, while carotid catheters resulted moderate or sever trauma. Therefore, it was suggested that it should not be set as hemorrhagic shock control model. As neutrophil L-selection expressions increased after trauma, the adhesion of leucocytes to the venule wall may be beneficial to the healing of wound and enhance the ability of anti-infection. The immediate increasing of neutrophil surface L-selectin expressions in this study was likely due to the direct release of Lselectin from cytoplasm granules that do not depend on protein synthesis.展开更多
Background: L-selectin (CD62L) is a cell surface adhesion molecule recently shown to play a critical role in determining endometrial receptivity and implantation in humans. By contrast, the L-selectin ligand is missin...Background: L-selectin (CD62L) is a cell surface adhesion molecule recently shown to play a critical role in determining endometrial receptivity and implantation in humans. By contrast, the L-selectin ligand is missing from the rodent endometrium. Interestingly, CD62L (L-selectin)-deficient BALB/c mice delivered significantly higher numbers of viable offspring than wild type controls via mechanisms yet to be defined. Methods: Nulliparous CD62L-deficient (8-10-week-old, n = 25) or wild type (n = 18) females were mated with 43 age-matched males. Animals were sacrificed at gestational day (GD) 9.5. Tissue samples were analyzed by immunostaining and flow cytometry. Results: Mating wild type and CD62L-deficient BALB/c mice revealed that the increased birth rate was due to the CD62L deficiency in females. Flow cytometric analysis demonstrated significant differences in the number of natural killer (NK) cells present in the uterus of pregnant CD62L- deficient mice compared to controls. Immunohistochemistry confirmed NK cell accumulation at the fetal-maternal interface. Discussion: Uterine NK cells have been shown to peak at GD 8-10 at the fetal-maternal interface. NK cells might regulate mouse fertility rates by facilitating development of the maternal spiral arteries, thereby stimulating the formation of larger vessels that facilitate intrauterine survival, however, their role is not obligate to spiral artery development. Conclusions: Diminished CD62L expression modified immune cell trafficking into the uterus of pregnant mice generating a microenvironment primarily dominated by NK cells resulting in improved embryonic survival rates.展开更多
L-selectin plays a crucial role in inflammation cascade by initiating the tethering and rolling of leukocytes on endothelium wall. While many L-selectin molecules are rapidly shed from the cell surface upon activation...L-selectin plays a crucial role in inflammation cascade by initiating the tethering and rolling of leukocytes on endothelium wall. While many L-selectin molecules are rapidly shed from the cell surface upon activation, the remaining membrane-anchored L-selectin may still play an important role in regulating leukocyte rolling and adhesion with different binding kinetics. Here we developed an in vitro model to activate Jurkat cells via interlukin-8 (IL-8) and quantified the two-dimensional (2D) binding kinetics, using a micropipette aspiration assay, of membrane-anchored L-selectin to P-selectin glycoprotein ligand 1 (PSGL-1) ligand coupled onto human red blood cells (RBCs). The data indicated that L-selectin shedding reduced the amount of membrane-anchored L-selectin and lowered both its reverse and forward rates. These results suggested that the rolling dynamics of activated leukocytes was determined by two opposite impacts: reducing the surface presentation would enhance the rolling but lowering the kinetic rates would decrease the rolling. This finding provides a new insight into under-standing how L-selectin shedding regulates leukocyte rolling and adhesion.展开更多
文摘Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Accumulaed evidence has suggested that heparin＇s anti-inflammatory effects are mainly mediated by blocking L-or P-selectin-initiated cell adhesion. Recently, we have reported that periodate-oxidized, borohydridereduced heparin （RO-heparln） can inhibit P-selectin-mediated acute inflammation. Here we further examined the effect of RO-heparin on the adhesion of L-selectin-mediated leukocytes to vascular endothelium under flow conditions in vivo and in vitro. The results show that RO-heparin with a low anticoagulant activity can effectively reduce leucocyte roiling on thioglycoUate-induced rat mesenterlc venules and L-selectin-metadiated neutrophil roiling on TNF-α-induced human umbilical vein endothelial cells（HUVECs） under flow conditions. Our findings suggest that the effect of RO-heparin on inflammatory responses is mainly a result of its inhibiting the interaction between P- or L-selectin and its ligands. The findings also suggest that RO-heparin may be useful in preventing inflammation diseases.
文摘Objective： To compare carotid catheters blooddrawing and tail-cut blooddrawing in traumatizing rats and changing their intemal L-selectin. Methods： Two ways of bloodletting were selected to produce hemorrhagic shock models. Monoclonal antibody sign and flow cytometer were used to test neutrophil L-selectin dynamic expression in rats. Results： No remarkable differences were shown among different time points in neutrophil L-selectin expressing amount （ average fluorescence index） （ P 〉 0.05）. Compared with the normal control group, all cell surface expressions in empirical control group increased. Cell surface expressions reached the summit at 3 hours and kept the high level at 4-5 hours. A progressive increase of the mRNA expression peaked at 5 hours; the expressions in both groups of carotid catheters blooddrawing increased compared with normal control group, and remained stable after 3 hours compared with the Tail-cut Blooddrawing Group. Conclusion： L-sclectin expressions changed little in tail-cut blooddrawing rats, while carotid catheters resulted moderate or sever trauma. Therefore, it was suggested that it should not be set as hemorrhagic shock control model. As neutrophil L-selection expressions increased after trauma, the adhesion of leucocytes to the venule wall may be beneficial to the healing of wound and enhance the ability of anti-infection. The immediate increasing of neutrophil surface L-selectin expressions in this study was likely due to the direct release of Lselectin from cytoplasm granules that do not depend on protein synthesis.
文摘Background: L-selectin (CD62L) is a cell surface adhesion molecule recently shown to play a critical role in determining endometrial receptivity and implantation in humans. By contrast, the L-selectin ligand is missing from the rodent endometrium. Interestingly, CD62L (L-selectin)-deficient BALB/c mice delivered significantly higher numbers of viable offspring than wild type controls via mechanisms yet to be defined. Methods: Nulliparous CD62L-deficient (8-10-week-old, n = 25) or wild type (n = 18) females were mated with 43 age-matched males. Animals were sacrificed at gestational day (GD) 9.5. Tissue samples were analyzed by immunostaining and flow cytometry. Results: Mating wild type and CD62L-deficient BALB/c mice revealed that the increased birth rate was due to the CD62L deficiency in females. Flow cytometric analysis demonstrated significant differences in the number of natural killer (NK) cells present in the uterus of pregnant CD62L- deficient mice compared to controls. Immunohistochemistry confirmed NK cell accumulation at the fetal-maternal interface. Discussion: Uterine NK cells have been shown to peak at GD 8-10 at the fetal-maternal interface. NK cells might regulate mouse fertility rates by facilitating development of the maternal spiral arteries, thereby stimulating the formation of larger vessels that facilitate intrauterine survival, however, their role is not obligate to spiral artery development. Conclusions: Diminished CD62L expression modified immune cell trafficking into the uterus of pregnant mice generating a microenvironment primarily dominated by NK cells resulting in improved embryonic survival rates.
基金Supported by the National Basic Research Program of China (Grant No. 2006CB910303)National Natural Science Foundation of China (Grant Nos. 30730032, 10332060)+1 种基金Knowledge Innovation Program of Chinese Academy of Sciences (Grant No. KJCX2-YW-L08)National High-Tech Research and De-velopment Program of China (Grant No. 2007AA02Z306)
文摘L-selectin plays a crucial role in inflammation cascade by initiating the tethering and rolling of leukocytes on endothelium wall. While many L-selectin molecules are rapidly shed from the cell surface upon activation, the remaining membrane-anchored L-selectin may still play an important role in regulating leukocyte rolling and adhesion with different binding kinetics. Here we developed an in vitro model to activate Jurkat cells via interlukin-8 (IL-8) and quantified the two-dimensional (2D) binding kinetics, using a micropipette aspiration assay, of membrane-anchored L-selectin to P-selectin glycoprotein ligand 1 (PSGL-1) ligand coupled onto human red blood cells (RBCs). The data indicated that L-selectin shedding reduced the amount of membrane-anchored L-selectin and lowered both its reverse and forward rates. These results suggested that the rolling dynamics of activated leukocytes was determined by two opposite impacts: reducing the surface presentation would enhance the rolling but lowering the kinetic rates would decrease the rolling. This finding provides a new insight into under-standing how L-selectin shedding regulates leukocyte rolling and adhesion.
