Granulocyte-macrophage colony-stimulating factor enhances cationic antimicrobial protein synthesis by human neutrophils

• Published in: The Journal of immunology (1950) Vol. 144; no. 9; pp. 3437 - 3443
• Main Authors: Waksman, Y, Golde, DW, Savion, N, Fabian, I
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.05.1990; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Antimicrobial Cationic Peptides; Biological and medical sciences; Blood Bactericidal Activity; Blood Proteins - biosynthesis; Chromatography, Ion Exchange; Colony-Stimulating Factors - pharmacology; Cycloheximide - pharmacology; Dactinomycin - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances - pharmacology; Humans; Hydroxyurea - pharmacology; Immunobiology; In Vitro Techniques; Lymphokines, interleukins ( function, expression); Molecular Weight; Neutrophils - metabolism; Puromycin - pharmacology; Regulatory factors and their cellular receptors; Human; Proteins; Leukocyte; Protein synthesis; Cytokine; Neutrophil; Antimicrobial agent; Granulocyte macrophage colony stimulating factor
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.144.9.3437

We analyzed the effect of recombinant human granulocyte macrophage CSF (GM-CSF) on protein synthesis in peripheral blood polymorphonuclear leukocytes. GM-CSF enhanced PMN 35S-methionine incorporation 1.5-fold over a 2-h incubation period. The effect of GM-CSF on the synthesis of specific proteins was investigated by separating the radiolabeled proteins on SDS-PAGE followed by autoradiography. Stimulation of protein synthesis by GM-CSF was rapid (2 h), dose dependent, and affected at least 10 separate polypeptides. Using ion exchange chromatography some of the GM-CSF-enhanced proteins were identified to have a cationic nature, including the 37- and the 57-kDA proteins whose synthesis was increased by GM-CSF 2.4-fold and 1.6-fold, respectively. The cationic protein fractions from GM-CSF-primed and control cells were eluted from an ion exchange column and tested for their antimicrobial activity. An overall twofold increase in the amount of cationic proteins was recovered from GM-CSF-treated cells as compared to control cells, and these proteins showed a proportional enhanced killing of S. typhimurium. These results suggest that enhanced cationic protein synthesis is an important mechanism whereby GM-CSF can increase neutrophil microbicidal activity via nonoxidative pathways.