Buescher E S, McIlheran S M, Banks S M, Vadhan-Raj S
Department of Pediatrics, University of Texas Health Science Center at Houston.
Exp Hematol. 1993 Oct;21(11):1467-72.
During a phase I trial of the genetically engineered hematopoietic growth factor PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 [IL-3] fusion protein), we examined the effects of PIXY321 treatment on human polymorphonuclear leukocyte (PMN) locomotive, respiratory burst, and phagocytic responses. PIXY321 treatment was associated with transient suppression of both unstimulated locomotion and chemotaxis responses to multiple stimuli, as well as significant transient enhancement of formyl peptide-stimulated H2O2 production. No effects on opsonic phagocytosis of Staphylococcus aureus were observed. In vitro exposure of control PMN to PIXY321 resulted in suppression of unstimulated locomotion/chemotaxis and enhancement of formyl peptide-stimulated H2O2 production but had no effects on phagocytosis. When patient cells were exposed in vitro to PIXY321 during treatment, suppression of chemotaxis and enhancement of H2O2 production were observed before PIXY321 treatment, but these effects diminished during treatment. The in vivo and in vitro exposure effects of PIXY321 treatment on PMN function are similar to those of the parent molecule, granulocyte-macrophage colony-stimulating factor (GM-CSF).
在基因工程造血生长因子PIXY321(粒细胞-巨噬细胞集落刺激因子/白细胞介素-3 [IL-3]融合蛋白)的I期试验中,我们研究了PIXY321治疗对人多形核白细胞(PMN)运动、呼吸爆发和吞噬反应的影响。PIXY321治疗与对多种刺激的未刺激运动和趋化反应的短暂抑制相关,以及甲酰肽刺激的H2O2产生的显著短暂增强。未观察到对金黄色葡萄球菌调理吞噬作用的影响。对照PMN在体外暴露于PIXY321导致未刺激运动/趋化的抑制和甲酰肽刺激的H2O2产生的增强,但对吞噬作用没有影响。当患者细胞在治疗期间在体外暴露于PIXY321时,在PIXY321治疗前观察到趋化抑制和H2O2产生增强,但这些作用在治疗期间减弱。PIXY321治疗对PMN功能的体内和体外暴露效应与母体分子粒细胞-巨噬细胞集落刺激因子(GM-CSF)相似。