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PAF-related analogues and their interaction with immunocomponent cells
PROSTAGLANDINS
PAF-RELATED ANALOGUES AND THEIR INTERACTION WITH IMMUNOCOMPETENT CELLS P. G. Munder, Max-Planck-lnstitut
M. Modolell,
and R. Andreesen
fiir Immunbiologie,
Freiburg
(FRG)
PAF-related analogues like 1-O-octadecyl-2-methoxy-3-phosphorylcholin (ALP) were first synthesized by our group in 1966/67 in an attempt to replace the mother compound lysophosphatidylcholin (2-LPC) as immunomodulating agent. While several of these compounds had indeed a much greater impact on the immune response than 2LPC, their most notable biological effect was an antitumor activity in vivo. In an attempt to clarify this antitumoral activity, two main activities were found : 1) A direct cytotoxic action on tumor cells mediated by a strong interference with the phospholipid metabolism of the membranes of tumor cells. 2) A transformation of normal inactive macrophages into highly active antitumoral effector cells. These ALP-transformed macrophages are able to destroy tumor cells completely in vitro within 48 to 70 hours. There is no need for cooperation with any other effector cells, nor any of the known lympho- or monokines. Nor does endotoxin play any synergic role. This transformation into cytotoxic effector cells is apparenty a two step mechanism and is strongly correlated in its effectiveness with the chemical structure of the PAF-related compound. The molecular basis of this transformation of normal macrophages into cytotoxic cells is, as yet, not understood. It has, however, to be pointed out that PAF or lyso-PAF themselves are not able to inhibit tumor growth in vivo or in vitro nor are these compounds able to generate cytotoxic macrophages. Although the difference might be explained by changes in the molecular structure there is still a gap of understanding in the biological efficacy which will be closed, hopefully, by future studies.
160
AUGUST 1987 VOL. 34 NO. 2
PAF-RELATED ANALOGUES AND THEIR INTERACTION WITH IMMUNOCOMPETENT CELLS P. G. Munder, Max-Planck-lnstitut
M. Modolell,
and R. Andreesen
fiir Immunbiologie,
Freiburg
(FRG)
PAF-related analogues like 1-O-octadecyl-2-methoxy-3-phosphorylcholin (ALP) were first synthesized by our group in 1966/67 in an attempt to replace the mother compound lysophosphatidylcholin (2-LPC) as immunomodulating agent. While several of these compounds had indeed a much greater impact on the immune response than 2LPC, their most notable biological effect was an antitumor activity in vivo. In an attempt to clarify this antitumoral activity, two main activities were found : 1) A direct cytotoxic action on tumor cells mediated by a strong interference with the phospholipid metabolism of the membranes of tumor cells. 2) A transformation of normal inactive macrophages into highly active antitumoral effector cells. These ALP-transformed macrophages are able to destroy tumor cells completely in vitro within 48 to 70 hours. There is no need for cooperation with any other effector cells, nor any of the known lympho- or monokines. Nor does endotoxin play any synergic role. This transformation into cytotoxic effector cells is apparenty a two step mechanism and is strongly correlated in its effectiveness with the chemical structure of the PAF-related compound. The molecular basis of this transformation of normal macrophages into cytotoxic cells is, as yet, not understood. It has, however, to be pointed out that PAF or lyso-PAF themselves are not able to inhibit tumor growth in vivo or in vitro nor are these compounds able to generate cytotoxic macrophages. Although the difference might be explained by changes in the molecular structure there is still a gap of understanding in the biological efficacy which will be closed, hopefully, by future studies.
160
AUGUST 1987 VOL. 34 NO. 2