Alfarsi Mohammed A, Hamlet Stephen M, Ivanovski Saso
Griffith Health Institute, Molecular basis of Disease Program and School of Dentistry and Oral Health, Griffith University, Gold Coast, Australia.
College of Dentistry, King Khalid University, Abha, Saudi Arabia.
Clin Implant Dent Relat Res. 2015 Dec;17(6):1036-47. doi: 10.1111/cid.12231. Epub 2014 Jun 6.
Platelets are one of the earliest cell types to interact with surgically inserted titanium implants. This in vitro study investigated the effect of titanium surface-induced platelet releasate on macrophage cytokine gene expression.
To mimic the in vivo temporal sequence of platelet arrival and protein production at the implant surface and the subsequent effect of these proteins on mediators of the immune response, the levels of platelet attachment and activation in response to culture on smooth polished, sandblasted and acid-etched (SLA), and hydrophilic-modified SLA (modSLA) titanium surfaces were first determined by microscopy and protein assay. The subsequent effect of the platelet-released proteins on human THP-1 macrophage cytokine gene expression was determined by polymerase chain reaction array after 1 and 3 days of macrophage culture on the titanium surfaces in platelet-releasate conditioned media.
Platelet attachment was surface dependent with decreased attachment observed on the hydrophilic (modSLA) surface. The platelet releasate, when considered independently of the surface effect, elicited an overall pro-inflammatory response in macrophage cytokine gene expression, that is, the expression of typical pro-inflammatory cytokine genes such as TNF, IL1a, IL1b, and CCL1 was significantly up-regulated whereas the expression of anti-inflammatory cytokine genes such as IL10, CxCL12, and CxCL13 was significantly down-regulated. However, following platelet exposure to different surface modifications, the platelet releasate significantly attenuated the macrophage pro-inflammatory response to microrough (SLA) titanium and hastened an anti-inflammatory response to hydrophilic (modSLA) titanium.
Theses results demonstrate that titanium surface topography and chemistry are able to influence the proteomic profile released by platelets, which can subsequently influence macrophage pro-inflammatory cytokine expression. This immunomodulation may be an important mechanism via which titanium surface modification influences osseointegration.
血小板是最早与外科植入的钛植入物相互作用的细胞类型之一。本体外研究调查了钛表面诱导的血小板释放物对巨噬细胞细胞因子基因表达的影响。
为模拟体内血小板到达植入物表面及蛋白质产生的时间顺序，以及这些蛋白质对免疫反应介质的后续影响，首先通过显微镜检查和蛋白质测定法确定了血小板在光滑抛光、喷砂和酸蚀（SLA）以及亲水性改性SLA（modSLA）钛表面培养时的附着和活化水平。在血小板释放物条件培养基中，将巨噬细胞在钛表面培养1天和3天后，通过聚合酶链反应阵列测定血小板释放的蛋白质对人THP-1巨噬细胞细胞因子基因表达的后续影响。
血小板附着具有表面依赖性，在亲水性（modSLA）表面观察到附着减少。当不考虑表面效应独立观察时，血小板释放物在巨噬细胞细胞因子基因表达中引发了总体促炎反应，即典型促炎细胞因子基因如TNF、IL1a、IL1b和CCL1的表达显著上调，而抗炎细胞因子基因如IL10、CxCL12和CxCL13的表达显著下调。然而，在血小板暴露于不同表面改性后，血小板释放物显著减弱了巨噬细胞对微粗糙（SLA）钛的促炎反应，并加速了对亲水性（modSLA）钛的抗炎反应。
这些结果表明，钛表面形貌和化学性质能够影响血小板释放的蛋白质组谱，进而影响巨噬细胞促炎细胞因子的表达。这种免疫调节可能是钛表面改性影响骨整合的重要机制。
