Walter R J, Danielson J R
J Natl Cancer Inst. 1987 Jan;78(1):61-9. doi: 10.1093/jnci/78.1.61.
Monocytes from patients with head and neck tumors display a marked chemotactic deficiency in response to formylpeptide chemoattractants. Normal leukocytes possess receptors known to bind to chemotactic formylpeptides such as the hexapeptide N-formyl-nor-leucyl-leucyl-phenylalanyl-nor-leucyl-tyrosyl-lysine, with high specificity and great avidity. Light microscopic autoradiography was used to visualize the binding and subsequent cellular processing of the formylhexapeptide N-formyl-nor-leucyl-leucyl-phenylalanyl-nor-leucyl-[125I]tyrosyl-lysine to polymorphonuclear leukocytes (PMN) and monocytes from patients with epidermoid tumors of the head and neck. Surface-adherent leukocytes were exposed to 5 nM 125I-labeled hexapeptide for 15 minutes at 4 degrees C and were either fixed immediately or rinsed and then further incubated for 20 minutes at 37 degrees C prior to fixation. Cells underwent autoradiography, and silver grains associated with 400 cells were counted. There were no significant differences between the numbers of formylpeptide receptors on control and cancer patient PMN. However, there were significantly larger numbers of formylpeptide receptors (P less than .02) on cancer patient monocytes than on control monocytes. Cells that were allowed to process bound hexapeptide at 37 degrees C prior to fixation showed large decreases in the number of cell-associated silver grains. However, the amount of hexapeptide associated with PMN and monocytes treated in this way was the same for both control and tumor patients. In addition, histograms were plotted showing the amount of hexapeptide bound versus the frequency of cells at each level of binding. Examination of these histograms revealed that two major peaks or subpopulations occurred in each for neutrophils and monocytes from control patients. Histograms of grain counts for neutrophils and monocytes from tumor patients did not display two separate peaks of formylhexapeptide binding; instead, only one broad peak was evident. These observations indicated that: Tumor patient PMN expressed as many formylpeptide receptors as did control PMN, and tumor patient monocytes possessed significantly more receptors than did control monocytes. The disposition of formylpeptide initially bound to control and tumor patient leukocytes appeared to be essentially the same. Subpopulations existed in each control neutrophil and monocyte sample, one exhibiting approximately 30% more formylpeptide binding than the other. However, in the leukocytes obtained from tumor patients, the distinction between these two subpopulations had become obscured such that only one cell population was evident.
头颈部肿瘤患者的单核细胞对甲酰肽趋化因子的反应表现出明显的趋化缺陷。正常白细胞拥有已知能与趋化性甲酰肽结合的受体，如六肽N-甲酰-去甲亮氨酰-亮氨酰-苯丙氨酰-去甲亮氨酰-酪氨酰-赖氨酸，具有高特异性和高亲和力。利用光学显微镜放射自显影技术来观察甲酰六肽N-甲酰-去甲亮氨酰-亮氨酰-苯丙氨酰-去甲亮氨酰-[125I]酪氨酰-赖氨酸与头颈部表皮样肿瘤患者的多形核白细胞（PMN）和单核细胞的结合及随后的细胞处理过程。将贴壁的白细胞在4℃下暴露于5 nM的125I标记六肽15分钟，然后立即固定，或者冲洗后在37℃下进一步孵育20分钟再固定。细胞进行放射自显影，并对与400个细胞相关的银颗粒进行计数。对照和癌症患者PMN上甲酰肽受体的数量没有显著差异。然而，癌症患者单核细胞上甲酰肽受体的数量显著多于对照单核细胞（P小于0.02）。在固定前于37℃下处理结合的六肽的细胞，其细胞相关银颗粒的数量大幅减少。然而，以这种方式处理的对照和肿瘤患者的PMN和单核细胞所结合的六肽量是相同的。此外，绘制了直方图，显示结合的六肽量与每个结合水平的细胞频率的关系。对这些直方图的检查显示，对照患者的中性粒细胞和单核细胞各自出现了两个主要峰值或亚群。肿瘤患者中性粒细胞和单核细胞的颗粒计数直方图没有显示甲酰六肽结合的两个单独峰值；相反，只有一个宽峰明显。这些观察结果表明：肿瘤患者的PMN表达的甲酰肽受体与对照PMN一样多，且肿瘤患者的单核细胞拥有的受体明显多于对照单核细胞。最初结合到对照和肿瘤患者白细胞上的甲酰肽的分布似乎基本相同。每个对照中性粒细胞和单核细胞样本中都存在亚群，其中一个亚群的甲酰肽结合量比另一个亚群多约30%。然而，在从肿瘤患者获得的白细胞中，这两个亚群之间的区别变得模糊，以至于只明显存在一个细胞群体。
