Immunoregulatory functions of paf-acether. IV. Enhancement of IL-1 production by muramyl dipeptide-stimulated monocytes.
paf-Acether (paf) is a phospholipid mediator of inflammation released from monocytes along with IL-1. In this study, we have examined the role of paf on IL-1 production by human monocytes. When paf from 1 nM to 5 microM, but not its precursor lyso paf, was added to monocytes in the presence of muramyl dipeptide (MDP) or LPS, a marked increase in IL-1 activity over the value with MDP alone was observed. In contrast, paf alone had minimal activity over the same dose range. Antibodies against rHu IL-1 alpha and rHu IL-1 beta neutralized the increased IL-1 activity. Interestingly, MDP that prompts monocytes to synthesize IL-1, induced the synthesis of paf, as well. Most of the paf produced remained cell-associated and always preceded IL-1 synthesis. When the paf receptor antagonist, L-652,731 was added to monocytes, it prevented the enhancement of IL-1 activity induced by exogenous paf. In contrast, L-652,731 had little effect on MDP-induced IL-1 synthesis in the absence of exogenous paf. This may indicate that there are alternative mechanisms involved in the sequences of events leading to IL-1 production. It is also conceivable that the paf receptor antagonist is not able to compete or inhibit endogenous paf as well as it does for exogenous paf. Nevertheless, exogenous paf in association with a second signal, modulates IL-1 production from human monocytes in a positive manner. This may constitute another means through which paf can modulate inflammatory and immune reactions.
Salem
P
P
Institut National de la Santé et de la Recherche Médicale, U200, Université Paris-Sud, Clamart, France.
Deryckx
S
S
Dulioust
A
A
Vivier
E
E
Denizot
Y
Y
Damais
C
C
Dinarello
C A
CA
Thomas
Y
Y
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology*; D012636:Secretory Rate / Q000187:drug effects
D007375:Interleukin-1; D010972:Platelet Activating Factor; D000001:Calcimycin; D000119:Acetylmuramyl-Alanyl-Isoglutamine