ABNORMALITIES OF POLYMORPHONUCLEAR LEUKOCYTE FUNCTION ASSOCIATED WITH A HERITABLE DEFICIENCY OF HIGH MOLECULAR-WEIGHT SURFACE GLYCOPROTEINS (GP138) - COMMON RELATIONSHIP TO DIMINISHED CELL ADHERENCE
ABNORMALITIES OF POLYMORPHONUCLEAR LEUKOCYTE FUNCTION ASSOCIATED WITH A HERITABLE DEFICIENCY OF HIGH MOLECULAR-WEIGHT SURFACE GLYCOPROTEINS (GP138) - COMMON RELATIONSHIP TO DIMINISHED CELL ADHERENCE
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DOI：
10.1172/jci111451
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发表时间：
1984-01-01
影响因子：
15.9
通讯作者：
SMITH, CW
中科院分区：
文献类型：
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作者：
ANDERSON, DC;SCHMALSTIEG, FC;SMITH, CW
对一名5岁的白人女性进行了中性粒细胞(PMN)功能的研究，该女性患有脐带分离延迟、脓液形成和PMN趋化性严重缺陷。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳法显示，患者的S细胞的颗粒和膜部分几乎完全缺乏高相对分子质量的糖蛋白(GP138)，NaB_3H_4-半乳糖氧化酶标记显示患者的中性粒细胞表面没有主要的糖蛋白复合体。用单克隆抗体(MAb)进行流式细胞仪检测，发现患者S患者外周血多形核细胞和单核细胞表面均未检测到已有的两种糖蛋白(MO1和LFA1)。用亚基特异性单抗对125I标记的患者细胞进行免疫沉淀，证实MO1的α-亚基(155kD[kD])和LFA1(177kD)及其共同的β-亚基(94kD)完全缺乏。对患者PMN的功能分析显示，黏附和黏附依赖的细胞功能严重受损，包括铺展、聚集、趋化梯度定向、抗体依赖的细胞毒性和对C3衍生配体选择性调节的颗粒(油红-0-石蜡、酵母多糖)的吞噬作用。患者PMN表现出与Ig G或C3b包被的绵羊红细胞的正常花环能力，但与C3b包被的红细胞的花环形成明显减少。黏附非依赖性功能，包括形状变化、N-甲酰甲硫基-亮氨酸-~3H-苯丙氨酸结合和可溶性刺激引起的O2-产生或分泌均正常。膜流动性、表面电荷和微管组装也正常。这些发现提供了新的证据，表明关键的PMN表面糖蛋白是促进炎症反应的多种黏附依赖细胞功能所必需的。
Investigations of polymorphonuclear leukocyte (PMN) function were performed in a 5-yr-old white female with delayed umbilical cord separation, impaired pus formation and a severe defect of PMN chemotaxis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated an almost total deficiency of a high MW glycoproteins(s) (GP138) in the granule and membrane fractions of the patient''s cells, and NaB3H4-galactose oxidase labeling demonstrated the absence of a major glycoprotein complex on the surface of her PMN. Monoclonal antibodies (MAb) were employed in flow cytometry experiments to demonstrate that 2 previously characterized glycoproteins (Mo1 and LFA1) were undetectable on the surfce of the patient''s PMN and monocytes. Immunoprecipitation of 125I-labeled patient cells with subunit specific MAb confirmed that the .alpha.-subunits of Mo1 (155 kD [kilodalton]) and LFA1 (177 kD) and their common .beta.-subunit (94 kD) were totally deficient. Functional analyses of patient PMN demonstrated severe impairment of adherence- and adhesion-dependent cell functions including spreading, aggregation, orientation in chemotactic gradients, antibody-dependent cellular cytotoxicity and phagocytosis of particles (Oil-Red-0-paraffin, zymosan) selectively opsonized with C3-derived ligands. Patient PMN demonstrated a normal capacity to rosette with IgG or C3b-coated sheep erythrocytes, but rosette formation with C3bi-coated erythrocytes was profoundly diminished. Adhesion-independent functions including shape change, N-formyl-methionyl-leucyl-3H-phenylalanine binding and O2- generation or secretion elicited by soluble stimuli were normal. Membrane fluidity, surface charge and microtuble assembly were also normal. These findings provide new evidence that critical PMN surface glycoproteins are required to facilitate multiple adhesion-dependent cellular functions of the inflammatory response.