Synergy between IL-8 and GM–CSF in reproductive tract epithelial cell secretions promotes enhanced neutrophil chemotaxis

• Published in: Cellular immunology Vol. 230; no. 1; pp. 23 - 32
• Main Authors: Shen, Li, Fahey, John V., Hussey, Stephen B., Asin, Susana N., Wira, Charles R., Fanger, Michael W.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.07.2004
• Subjects: Antibodies - immunology; Antibodies - pharmacology; Cells, Cultured; Cervix; Chemokine; Chemotaxis; Chemotaxis - drug effects; Culture Media, Conditioned - chemistry; Culture Media, Conditioned - pharmacology; Drug Synergism; Endometrium; Epithelial Cells - secretion; Fallopian tube; Female; Genitalia, Female - cytology; Genitalia, Female - secretion; GM–CSF; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor - secretion; Humans; IL-8; Interleukin-8 - antagonists & inhibitors; Interleukin-8 - metabolism; Interleukin-8 - pharmacology; Interleukin-8 - secretion; Neutralizing antibody; Neutrophil; Neutrophils - cytology; Neutrophils - drug effects; Chemokine; GM–CSF; Neutrophil; IL-8; Fallopian tube; Cervix; Chemotaxis; Endometrium; Neutralizing antibody
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2004.08.004

Neutrophils occur in tissues of the female reproductive tract (FRT) under non-infected conditions. These cells generally enter tissues under the influence of chemoattractants called chemokines. Primary epithelial cells (EC) from FRT were a potent source of chemokines, IL-8 being the chief neutrophil chemoattractant secreted. Blocking with neutralizing anti-IL-8 showed that IL-8 did not account for all of the chemoattraction observed. A mixture of 25 ng/mL rIL-8 and 1 ng/mL rGM-CSF mediated 2.7-fold more chemotaxis than that expected if the two agents were additive. We then found that GM–CSF was produced by EC in amounts that synergised strongly with IL-8 to enhance chemotaxis. Treatment of uterine EC conditioned medium with saturating doses of anti-IL-8 plus anti-GM–CSF antibodies produced an 84% inhibition of chemotaxis, These findings demonstrate that the majority of neutrophil chemoattractant activity produced by FRT EC results from the synergistic effects of IL-8 and GM–CSF.