Synergy between IL-8 and GM-CSF in reproductive tract epithelial cell secretions promotes enhanced neutrophil chemotaxis.
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.
Shen
Li
L
Department of Immunology and Microbiology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756, USA. lilian.shen@dartmouth.edu
Fahey
John V
JV
Hussey
Stephen B
SB
Asin
Susana N
SN
Wira
Charles R
CR
Fanger
Michael W
MW
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004357:Drug Synergism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005836:Genitalia, Female / Q000166:cytology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects
D000906:Antibodies; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D016178:Granulocyte-Macrophage Colony-Stimulating Factor