Tumor necrosis factor release by human monocytes stimulated with platelet-activating factor.
Platelet-activating factor (PAF) is a low molecular weight phospholipid which enhances human monocyte cytotoxicity for tumor cells. In the current studies, the capacity of PAF to stimulate release of tumor necrosis factor alpha (TNF alpha) by human monocytes was assessed. PAF induced maximal TNF alpha synthesis 2-3 hr after monocyte stimulation as assessed by dot blotting of cell-associated TNF alpha using polyclonal anti-TNF antibody. Maximal net release of TNF alpha occurred 5-16 hr after monocyte stimulation, as assessed by a specific ELISA. Dose-response studies revealed that a maximal two- to three-fold increase in release of TNF alpha occurs at 10-100 pM PAF. LysoPAF and the optical isomer of PAF did not stimulate release of TNF alpha, suggesting that stimulation is mediated by specific PAF receptors. Scatchard analysis of [3H]PAF binding to monocyte membranes revealed 651 +/- 495 binding sites/monocyte with a Kd of 4.7 +/- 4.2 x 10(-10) M. PAF is a structurally unique activator of monocytes whose interactions with TNF alpha and other cytokines may be critical to host defense against tumors.
Ruis
N M
NM
Department of Medicine, Veterans Administration Medical Center, San Francisco, California 94121.
Rose
J K
JK
Valone
F H
FH
D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor