Abstract

Dialyzable leukocyte extracts (DLE) prepared from peripheral blood leukocytes obtained from normal human donors have several effects on the migration of polymorphonuclear neutrophils (PMN). Previously, we proposed that one or more of these effects might be mediated at least in part by prostaglandins (PG). In the present study we present results which indicate that an antigen-independent enhancement of PMN migration (ELM) induced by a still unidentified component in DLE may be caused by de novo synthesis of PG. This ELM was abolished by preincubation of PMN with noncytotoxic concentrations of indomethacin, mefenamic acid, ibuprofen, or eicosatetraynoic acid, and in agreement with other studies, we found that PGEs or PGFs could enhance random PMN migration. We also found that an antigen-dependent ELM can be produced by PGA. The levels of PGA and of PGE and F in crude DLE preparations were determined by radioimmunoassay and found to be within the range of concentrations required for the in vitro effects noted. The two effects produced by PGA and PGE or F might tend to suppress or otherwise modify antigen-dependent LMI activity in vivo, especially at local inflammatory foci produced by injection of DLE when used for immunotherapy. Future studies seem warranted to determine whether PG levels should be altered in DLE for more effective immunotherapy, and to further investigate the effects of PG or related metabolites on LMI and associated aspects of cell-mediated immunity.

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