Human fibroblasts maintain the viability and augment the functional response of human neutrophils in culture.
When human neutrophils were co-cultured for 72 h with nontransformed human fibroblasts, 69 +/- 3% (n = 13) survived, as compared with survival levels of 2 +/- 1% (n = 15) and 26 +/- 6% (n = 7), respectively, for neutrophils cultured for the same time period in enriched medium alone or supplemented with 10 pM recombinant human granulocyte/macrophage colony-stimulating factor (rh GM-CSF). Conditioned medium from the human fibroblast cultures enhanced neutrophil survival in a dose-dependent fashion to the same level achieved with neutrophil/fibroblast co-cultures, and its soluble viability-sustaining activity was not inhibited by preincubation with neutralizing antiserum against rh GM-CSF. As compared with freshly isolated replicate samples, neutrophils co-cultured with human fibroblasts for 72 h exhibited augmented FMLP-stimulated superoxide production without spontaneous superoxide generation. This striking extension of survival and associated priming for a ligand response by neutrophils co-cultured with human fibroblasts suggests that fibroblasts may contribute to the proinflammatory properties of neutrophils in tissues.
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
C J
CJ
Ling
W F
WF
Owen
K F
KF
Austen
D002470:Cell Survival; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D011994:Recombinant Proteins; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor