Ghio Massimo, Ottonello Luciano, Contini Paola, Amelotti Massimo, Mazzei Clemente, Indiveri Francesco, Puppo Francesco, Dallegri Franco
Department of Internal Medicine and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Italy.
Blood. 2003 Aug 1;102(3):1100-7. doi: 10.1182/blood.V102.3.1100.
Studies comparing transfusion and nontransfusion patients suggest an increased risk of postoperative infections in transfusion groups. Supernatants of blood components have been shown to affect the function of T lymphocytes and natural killer cells. Here, we found that supernatants from stored red blood cells (RBCs) inhibit human neutrophil migration in response to formyl peptides and stimulate neutrophil locomotion. These effects can be observed with high dilutions of RBC supernatants, such as 1:5 x 106 (vol/vol), able to trigger locomotion as well as desensitization of the cells to alternative chemoattractants. The phenomenon might be mediated by chemoattractants present in the supernatants. As RBC supernatants failed to mobilize intracellular free calcium, the chemoattractants should belong to the group of pure chemoattractants, that is, soluble Fas ligand (sFasL) and transforming growth factor-beta1 (TGF-beta1), known to act without increasing calcium levels. Recombinant TGF-beta1, but not sFasL, was found to reproduce the ability of RBC supernatants to both inhibit neutrophil response to formyl peptides and stimulate neutrophil locomotion. Moreover, TGF-beta1-immunodepleted supernatants did not display neutrophil-directed activities. Finally, RBC supernatants from RBCs stored after depletion of leukocytes were incapable of affecting neutrophil function. With neutrophils acting as a first-line antimicrobial defense, the ability, shown here, of high dilutions of RBC supernatants to inhibit neutrophil chemotaxis through TGF-beta1 may be a relevant determinant of infections in the postoperative period for transfusion patients. Consistently, the neutrophil chemotactic response to formyl peptide was inhibited by the plasma obtained from 5 transfusion patients.
比较输血患者和非输血患者的研究表明，输血组术后感染风险增加。血液成分的上清液已被证明会影响T淋巴细胞和自然杀伤细胞的功能。在此，我们发现储存红细胞（RBC）的上清液会抑制人类中性粒细胞对甲酰肽的迁移，并刺激中性粒细胞运动。在高稀释度的RBC上清液中可以观察到这些效应，例如1:5×106（体积/体积），其能够触发细胞运动以及使细胞对其他趋化因子脱敏。这种现象可能由上清液中存在的趋化因子介导。由于RBC上清液未能动员细胞内游离钙，这些趋化因子应属于纯趋化因子组，即可溶性Fas配体（sFasL）和转化生长因子-β1（TGF-β1），已知它们在不增加钙水平的情况下发挥作用。发现重组TGF-β1而非sFasL能够重现RBC上清液抑制中性粒细胞对甲酰肽反应并刺激中性粒细胞运动的能力。此外，TGF-β1免疫耗尽的上清液未表现出针对中性粒细胞的活性。最后，白细胞耗尽后储存的RBC的上清液无法影响中性粒细胞功能。由于中性粒细胞作为一线抗菌防御，本文所示的高稀释度RBC上清液通过TGF-β1抑制中性粒细胞趋化性的能力可能是输血患者术后感染的一个相关决定因素。同样，从5名输血患者获得的血浆抑制了中性粒细胞对甲酰肽的趋化反应。
