Granulopoietic inhibitors excreted in the urine of a patient with uterine cancer and marked leukocytosis.
An inhibitor of colony stimulating factor (CSF) was found in normal human urine and in the urine of a patient with uterine cancer and leukocytosis. The amount of inhibitor excreted in the patient's urine was inversely related to the amount of CSF excreted. Since the patient's urine contained the inhibitor in large amounts, it was used for further characterization of the inhibitor. The inhibitor was separated from CSF by DEAE-cellulose column chromatography, and precipitated by ammonium sulfate and 30-80% saturation. The result of centrifugation of the inhibitor in a NaBr solution of d = 1.21 and extraction of its solution by chloroform suggested that it is not a lipoprotein. Furthermore, it was inactivated by heating at 60 degree C. Isoelectrofocusing resolved in into two peaks of pI 6.7-8.4 (pI-7 inhibitor) and pI 4.7-5.4 (pI-5 inhibitor), both of which showed an apparent molecular weight of 80,000-90,000 upon Sephadex G-100 chromatography. Dose-response relation for CSF in the presence of the inhibitor(s) showed that the action of the inhibitor(s) was not due to specific inactivation of CSF. Both pI-05 and pI-7 inhibitor fractions showed mitogenic activity to mouse spleen cells in culture, and only slightly inhibited [3H]thymidine uptake in the PHA or LPS stimulated spleen lymphocytes. The result suggests that the granulopoietic inhibitor(s) obtained above is not a non-specifically cytotoxic substance(s).
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000652:urine*; D002499:Centrifugation, Density Gradient; D003115:Colony-Stimulating Factors / Q000037:antagonists & inhibitors* / Q000652:urine; D005260:Female; D005590:Fractional Precipitation; D006098:Granulocytes; D006801:Humans; D007525:Isoelectric Focusing; D007964:Leukocytosis / Q000150:complications / Q000652:urine*; D008214:Lymphocytes / Q000187:drug effects; D008970:Molecular Weight; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000652:urine*
D003115:Colony-Stimulating Factors