Deree Jessica, Lall Rohan, Melbostad Heidi, Grant Michael, Hoyt David B, Coimbra Raul
Division of Trauma and Surgical Critical Care, Department of Surgery, University of California San Diego School of Medicine, San Diego, CA, USA.
J Surg Res. 2006 Jun 1;133(1):22-8. doi: 10.1016/j.jss.2006.02.031.
Neutrophils play a major role as the first line in host defense after exposure to bacterial products. However, an exaggerated inflammatory response characterized by overwhelming neutrophil activation can be injurious to the host. Pentoxifylline (PTX), a nonspecific phosphodiesterase inhibitor, has been shown to attenuate neutrophil oxidative burst and decrease proinflammatory mediator synthesis. We hypothesized that PTX down-regulates neutrophil activation by decreasing the surface expression of both CD35 and CD66b, two markers of neutrophil degranulation.
Venous blood was obtained from three healthy volunteers. Whole blood was incubated with HBSS (control), f-methionyl-leucyl-phenylalanine (fMLP, 1 microM/L), PTX (2 mM/L), or fMLP + PTX. CD35 and CD66b expression were measured by flow cytometry.
fMLP treatment caused a significant increase in CD35 and CD66b expression of when compared to controls (P < 0.01). PTX treatment revealed expression of both markers comparable to the control group. A 38% decrease in CD35 (64 +/- 12 versus 100; P < 0.01) and a 52% decrease in CD66b (48 +/- 7 versus 100; P < 0.01) expression were demonstrated in the fMLP + PTX group when compared to fMLP alone.
In addition to the known effects of PTX on neutrophil oxidative burst, PTX also affects neutrophil degranulation, an essential step in enzyme release and subsequent tissue injury. These findings may have clinical relevance in the treatment of disease processes due to inflammation in which primed neutrophils play a role.
中性粒细胞在接触细菌产物后作为宿主防御的第一道防线发挥主要作用。然而，以中性粒细胞过度激活为特征的过度炎症反应可能对宿主造成伤害。己酮可可碱（PTX）是一种非特异性磷酸二酯酶抑制剂，已被证明可减弱中性粒细胞的氧化爆发并减少促炎介质的合成。我们假设PTX通过降低中性粒细胞脱颗粒的两个标志物CD35和CD66b的表面表达来下调中性粒细胞的激活。
从三名健康志愿者采集静脉血。全血与HBSS（对照）、f-甲硫氨酰-亮氨酰-苯丙氨酸（fMLP，1微摩尔/升）、PTX（2毫摩尔/升）或fMLP + PTX一起孵育。通过流式细胞术测量CD35和CD66b的表达。
与对照组相比，fMLP处理导致CD35和CD66b表达显著增加（P < 0.01）。PTX处理显示这两种标志物的表达与对照组相当。与单独使用fMLP相比，fMLP + PTX组中CD35表达降低了38%（64 ± 12对100；P < 0.01），CD66b表达降低了52%（48 ± 7对100；P < 0.01）。
除了PTX对中性粒细胞氧化爆发的已知作用外，PTX还影响中性粒细胞脱颗粒，这是酶释放和随后组织损伤的关键步骤。这些发现可能在治疗由炎症引起的疾病过程中具有临床相关性，在这些疾病中预激活的中性粒细胞起作用。
