A neutrophil derived factor(s) stimulates [3H]thymidine incorporation by vascular smooth muscle cells in vitro.
There is increasing evidence for the involvement of inflammatory cells in the development of intimal hyperplasia. This study examines the effect of human neutrophils on the incorporation of [3H]-thymidine into acid precipitable materials (DNA) in cultured rabbit vascular smooth muscle cells. Co-culture of intact neutrophils and vascular smooth muscle cells caused [3H]-thymidine incorporation by these cells to increase 209 +/- 22% (mean +/- SEM) of control. Sonication of the neutrophils abolished this effect (117 +/- 10%). Neutrophil conditioned medium prepared in the presence or absence of fetal calf serum had a similar effect on [3H]-thymidine incorporation by vascular smooth muscle cells (204 +/- 20% and 172 +/- 17% respectively). Stimulation of neutrophils with either Concanavalin A or serum-activated zymosan failed to increase production of the factor(s). The neutrophil derived factor(s) prepared in minimal essential medium was partially stable at 56 degrees C, but inactivated by boiling. Dialysis (pore size 12,000-14,000) did not remove the factor(s). Cyclooxygenase inhibition with indomethacin did not inhibit production of the factor(s) by neutrophils, but indomethacin caused an increase in [3H]-thymidine incorporation by vascular smooth muscle cells (181 +/- 11%). Indomethacin together with intact neutrophils had an additive effect on [3H]-thymidine incorporation (273 +/- 42%) into cellular DNA. These data show that neutrophils produce a factor(s) that stimulates [3H]-thymidine incorporation into DNA by vascular smooth muscle cells and suggests that vascular smooth muscle proliferation and intimal hyperplasia may be initiated by neutrophils adherent to sites of endothelial injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Cole
C W
CW
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Makhoul
R G
RG
McCann
R L
RL
O'Malley
M K
MK
Hagen
P O
PO
D000818:Animals; D001013:Aorta, Thoracic; D001769:Blood; D002455:Cell Division; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits; D013936:Thymidine / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D003208:Concanavalin A; D004247:DNA; D015054:Zymosan; D013936:Thymidine; D007213:Indomethacin