N-formylmethionyl-leucyl-phenylalanine, a potent chemotactic peptide for human polymorphonuclear leukocytes, is less chemotactic for human blood monocytes. Esterification of the N-formylated tripeptide enhances its chemotactic activity for monocytes by more than 4 logs, whereas a decrease by 3 logs is observed for polymorphonuclear leukocytes. These results indicate the participation of the C-terminal carboxyl group in chemotaxis of different cell types. We have also observed the selective inhibition of chemotactic responsiveness of human blood monocytes by a clinically useful antirheumatic drug, sodium aurothiomalate. Since this is the first in vitro cell migration model of inflammation in which gold compounds have demonstrated activity in micromolar concentrations, it suggests a site of action for this antirheumatic drug.In 1975 Schiffman et al. reported that a number of small synthetic N-formylmethionyl peptides were strongly chemotactic for both neutrophils and macrophages (1). They subsequently found that the N-formyl tripeptides were more effectivc: than dipeptides in their chemotactic activity, lysosomal enzyme-releasing ability in rabbit neutrophils (2), histamine-releasing ability in human basophils (3), and receptor binding on rabbit neutrophils (4). However, it is not clear whether these tripeptides are equally active in chemotaxis against both human polymorphonuclear leukocytes (PMN) and blood monocytes (MNC). We are. now reporting that the formylated tripeptides are poor chemoattractants for MNC and that esterification of the formylated tripeptides increases their chemotactic activity against MNC by more than four orders of magnitude. In addition, several antiinflammatory and antirheumatic drugs were examined for their inhibitory activity in chemotaxis of PMN and MNC.
MATERIALS AND METHODSN-formylmethionyl-leucyl-phenylalanine (FM LP) was obtained from Bachem (Marina Del Rey. California). The methyl ester of FMLP (FMLP-M) was synthesized by routine methods of peptide synthesis; M P 132-135'; [ylDZh-19.4 (C = 0.5, DMF); C,H,S elemental analysis within 0.3% of theory: chromatographically pure in two standard solvent systems for peptides (5). Sodium aurothiomalate was obtained from Aldrich Chemicals and sodium aurothioglucose from Sigma Chemicals.Blood was drawn in sterile syringes with 0.38% of sodium citrate/ml of blood from healthy human volunteers who had not ingested any antiinflammatory drugs including aspirin for at least 7 days. After low-speed centrifugation (200 X g for 15 minutes), the platelet-enriched plasma was removed and the cells were resuspended in Dulbecco's phosphate-buffered saline (Grand Island Biological Co, Grand Island, New
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