P-selectin support of neonatal neutrophil adherence under flow: Contribution of L-selectin, LFA-1, and ligand(s) for P-selectin
P-selectin support of neonatal neutrophil adherence under flow: Contribution of L-selectin, LFA-1, and ligand(s) for P-selectin
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DOI：
10.1182/blood.v91.12.4776.412k32_4776_4785
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发表时间：
1998-06-15
期刊：
影响因子：
20.3
通讯作者：
Smith, CW
中科院分区：
文献类型：
--
作者：
Mariscalco, MM;Tcharmtchi, MH;Smith, CW
为了进一步确定新生儿中性粒细胞与成人细胞相比定位于炎症组织的能力，我们在两种条件下检查了新生儿中性粒细胞与p-选择素单层的相互作用：(1)在恒定剪切应力和流动下的附着；(2)脱离，细胞在没有剪切应力的情况下附着，然后引入剪切应力并逐步增加。在2 dynes/cm的恒定剪切应力下，脐带血和成人中性粒细胞与未受刺激的人脐静脉内皮细胞（HUVECs）的相互作用最小(2)。组胺刺激后，新生儿和成体细胞与HUVECs相互作用（相互作用细胞=滚动+阻滞）的数量均显著增加，但新生儿仅为成体的40% （P < 0.05）。新生儿中性粒细胞与转染人P-选择素（CHO-P-选择素；成人值的60%，P < 0.003）的中国仓鼠卵巢（CHO）细胞单层的相互作用也显著降低。在相互作用的细胞中，与成人细胞相比，在受刺激的HUVECs和cho - p选择素的作用下，新生细胞滚动的比例较低。新生儿中性粒细胞l -选择素对p -选择素的附着减少有以下支持：(1)新生儿中性粒细胞l -选择素的表达显著降低。(2)抗l -选择素单克隆抗体可使相互作用的成年中性粒细胞数量减少到未治疗的新生儿中性粒细胞水平，但对新生儿中性粒细胞无影响。相比之下，l -选择素似乎在维持新生儿或成人中性粒细胞的相互作用中没有作用。一旦发生附着，新生儿中性粒细胞与p -选择素单层的相互作用在较小程度上依赖于LFA-1和其他配体，基于以下原因：(1)与成年中性粒细胞相比，对照组新生儿中性粒细胞的滚动分数降低，尽管相互作用的中性粒细胞总数在两组之间相等。(2)抗lfa - 1治疗导致新生儿和成人中性粒细胞滚动分数增加。然而，尽管相互作用的成年中性粒细胞数量保持不变，但新生儿中性粒细胞数量随着剪切应力的增加而减少。我们推测这种新生儿细胞分离的增加是由于中性粒细胞配体与p选择素的差异。(C) 1998年由美国血液病学会出版。
To further define the neonatal neutrophil's ability to localize to inflamed tissue compared with adult cells, we examined the neonatal neutrophil interactions with P-selectin monolayers under two conditions: (1) attachment under constant shear stress and flow and (2) detachment where cells were allowed to attach in the absence of shear stress and then shear stress is introduced and increased in step-wise increments. Cord blood and adult neutrophils had minimal interactions with unstimulated human umbilical vein endothelial cells (HUVECs) at a constant shear stress of 2 dynes/cm(2). There was a marked increase in the number of both neonatal and adult cells interacting (interacting cells = rolling + arresting) with HUVECs after histamine stimulation, although the neonatal value was only 40% of adult (P < .05). Neonatal neutrophils also had significantly decreased interaction with monolayers of Chinese hamster ovary (CHO) cells transfected with human P-selectin (CHO-P-selectin; 60% of adult values, P < .003). Of the interacting cells, there was a lower fraction of neonatal cells that rolled compared with adult cells on both stimulated HUVECs and CHO-P-selectin. That neonatal neutrophil L-selectin contributes to the diminished attachment to P-selectin is supported by the following: (1) Neonatal neutrophils had significantly diminished expression of L-selectin. (2) Anti-L-selectin monoclonal antibody reduced the number of interacting adult neutrophils to the level seen with untreated neonatal neutrophils, but had no effect on neonatal neutrophils. In contrast, L-selectin appeared to play no role in maintaining the interaction of either neonatal or adult neutrophils in the detachment assay. Once attachment occurred, the neonatal neutrophil's interaction with the P-selectin monolayer was dependent on LFA-1 and to other ligands to a lesser degree based on the following: (1) Control neonatal neutrophils had decreased rolling fraction compared with adult neutrophils, although the total number of interacting neutrophils was equal between groups. (2) Anti-LFA-l treatment resulted in an increase in the rolling fraction of both neonatal and adult neutrophils. However, whereas the number of interacting adult neutrophils remained unchanged, the number of neonatal neutrophils decreased with increased shear stress. We speculate that this increased detachment of neonatal cells is due to differences in neutrophil ligand(s) far P-selectin. (C) 1998 by The American Society of Hematology.