Differential induction of apoptosis by Fas-Fas ligand interactions in human monocytes and macrophages.
Human monocytes undergo spontaneous apoptosis upon culture in vitro; removal of serum from the media dramatically increases the rate of this process. Monocyte apoptosis can be significantly abrogated by the addition of growth factors or proinflammatory mediators. We have evaluated the role of the endogenous Fas-Fas ligand (FasL) interaction in the induction of this spontaneous apoptosis and found that a Fas-immunoglobulin (Ig) fusion protein, an antagonistic anti-Fas monoclonal antibody and a rabbit anti-FasL antibody all greatly reduced the onset of apoptosis. The results indicate that spontaneous death of monocytes is mediated via an autocrine or paracrine pathway. Treatment of the cells with growth factors or cytokines that prevented spontaneous apoptosis had no major effects on the expression of Fas or FasL. Additionally, monocyte-derived macrophages were found to express both Fas and FasL but did not undergo spontaneous apoptosis and were not sensitive to stimulation by an agonistic anti-Fas IgM. These results indicate that protective mechanisms in these cells exist at a site downstream of the receptor-ligand interaction.
Kiener
P A
PA
Immunological Diseases, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
Davis
P M
PM
Starling
G C
GC
Mehlin
C
C
Klebanoff
S J
SJ
Ledbetter
J A
JA
Liles
W C
WC
D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D053938:DNA Fragmentation; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D009000:Monocytes / Q000166:cytology*; D013997:Time Factors; D019014:fas Receptor / Q000502:physiology*
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor