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. 1980 Jul;69(3):473–478. doi: 10.1111/j.1476-5381.1980.tb07037.x

The effects of some antirheumatic drugs on an in vitro model of human polymorphonuclear leucocyte chemokinesis.

M J Smith, J R Walker
PMCID: PMC2044286  PMID: 7397456

Abstract

1 A rapid, reproducible in vitro assay for studying the chemokinetic movement of human polymorphonuclear leucocytes (PMNs) is described. Two synthetic peptides, formyl methionyl-leucyl-phenylalanine (FMLP) and formyl methionyl-phenylalanine (FMP), were used as a standard chemokinesins. 2 Maximal chemokinetic movement was observed with peptide concentrations of 2.5 nM (FMLP) and 100 muM (FMP). EC50 values of 650.0 +/- 60.0 pM and 27.0 +/- 3.5 muM respectively are similar to those reported for chemotactic activity of the peptides in micropore filter assays. 3 The PMN chemokinetic response to FMLP was enhanced by histamine (100 nM) and vitamin C (2.5 muM). 4 Human serum albumin was shown to induce chemokinesis but to antagonize the response to FMLP in a dose-related fashion. Fibrinogen similarly antagonized the cell response to peptide. 5 Levamisole (250 nM to 2.5 muM) significantly potentiated the chemokinetic responses to FMLP and FMP in a dose-related manner. The chemokinetic response to FMLP was unaffected by D-penicillamine (250 muM to 10 mM) while alclofenac (500 muM to 1 mM), salicylic acid (250 muM to 10 mM) and indomethacin (100 muM to 1 mM) caused dose-related inhibition.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson R., Glover A., Koornhof H. J., Rabson A. R. In vitro stimulation of neutrophil motility by levamisole: maintenance of cgmp levels in chemotactically stimulated levamisole-treated neutrophils. J Immunol. 1976 Aug;117(2):428–432. [PubMed] [Google Scholar]
  2. Anderson R., Glover A., Rabson A. R. The in vitro effects of histamine and metiamide on neutrophil motility and their relationship to intracellular cyclic nucleotide levels. J Immunol. 1977 May;118(5):1690–1696. [PubMed] [Google Scholar]
  3. Borel J. F. Effect of some drugs on the chemotaxis of rabbit neutrophils in vitro. Experientia. 1973 Jun 15;29(6):676–678. doi: 10.1007/BF01944767. [DOI] [PubMed] [Google Scholar]
  4. Brown K. A., Collins A. J. Action of nonsteroidal, anti-inflammatory drugs on human and rat peripheral leucocyte migration in vitro. Ann Rheum Dis. 1977 Jun;36(3):239–243. doi: 10.1136/ard.36.3.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown K. A., Collins A. J. In vitro effects of non-steroidal anti-inflammatory drugs on human polymorphonuclear cells and lymphocyte migration. Br J Pharmacol. 1978 Nov;64(3):347–352. [PMC free article] [PubMed] [Google Scholar]
  6. Chwalinska-Sadowska H., Baum J. The effect of D-penicillamine on polymorphonuclear leukocyte function. J Clin Invest. 1976 Oct;58(4):871–879. doi: 10.1172/JCI108540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cunningham F. M., Ford-Hutchinson A. W., Oliver A. M., Smith M. J., Walker J. R. The effects of D-pencillamine and levamisole on leucocyte chemotaxis in the rat. Br J Pharmacol. 1978 May;63(1):119–123. doi: 10.1111/j.1476-5381.1978.tb07781.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. GEORGE M., VAUGHAN J. H. In vitro cell migration as a model for delayed hypersensitivity. Proc Soc Exp Biol Med. 1962 Nov;111:514–521. doi: 10.3181/00379727-111-27841. [DOI] [PubMed] [Google Scholar]
  9. Goetzl E. J., Wasserman S. I., Gigli I., Austen K. F. Enhancement of random migration and chemotactic response of human leukocytes by ascorbic acid. J Clin Invest. 1974 Mar;53(3):813–818. doi: 10.1172/JCI107620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harrington J. T., Jr, Stastny P. Macrophage migration from an agarose droplet: development of a micromethod for assay of delayed hypersensitivity. J Immunol. 1973 Mar;110(3):752–759. [PubMed] [Google Scholar]
  11. Lambelin G., Roba J., Gillet C., Buu-Hoï N. P. Pharmacology of a new analgesic, antipyretic, and anti-inflammatory agent, 4-allyloxy-3-chlorophenylacetic acid. Arzneimittelforschung. 1970 May;20(5):610–618. [PubMed] [Google Scholar]
  12. Maderazo E. G., Woronick C. L. Micropore filter assay of human granulocyte locomotion: problems and solutions. Clin Immunol Immunopathol. 1978 Oct;11(2):196–211. doi: 10.1016/0090-1229(78)90044-2. [DOI] [PubMed] [Google Scholar]
  13. Meacock S. C., Kitchen E. A. Some effects of non-steroidal anti-inflammatory drugs on leucocyte migration. Agents Actions. 1976 Feb;6(1-3):320–325. doi: 10.1007/BF01972249. [DOI] [PubMed] [Google Scholar]
  14. Mowat A. G. Neutrophil chemotaxis in rheumatoid arthritis. Effect of D-penicillamine, gold salts, and levamisole. Ann Rheum Dis. 1978 Feb;37(1):1–8. doi: 10.1136/ard.37.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mukherjee C., Lynn W. S. Role of ions and extracellular protein in leukocyte motility and membrane ruffling. Am J Pathol. 1978 Nov;93(2):369–381. [PMC free article] [PubMed] [Google Scholar]
  16. O'Flaherty J. T., Kreutzer D. L., Showell H. J., Vitkauskas G., Becker E. L., Ward P. A. Selective neutrophil desensitization to chemotactic factors. J Cell Biol. 1979 Mar;80(3):564–572. doi: 10.1083/jcb.80.3.564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Repine J. E., Clawson C. C. Influence of surface proteins and separation techniques on neutrophil unstimulated and stimulated locomotion in vitro. J Reticuloendothel Soc. 1978 Sep;24(3):217–226. [PubMed] [Google Scholar]
  18. Rivkin I., Foschi G. V., Rosen C. H. Inhibition of in vitro neutrophil chemotaxis and spontaneous motility by anti-inflammatory agents. Proc Soc Exp Biol Med. 1976 Nov;153(2):236–240. doi: 10.3181/00379727-153-39518. [DOI] [PubMed] [Google Scholar]
  19. Rivkin I. The effect of bovine serum albumin on the in vitro inhibition of chemotaxis by anti-inflammatory agents. Agents Actions. 1977 Oct;7(4):465–468. doi: 10.1007/BF01966854. [DOI] [PubMed] [Google Scholar]
  20. Showell H. J., Freer R. J., Zigmond S. H., Schiffmann E., Aswanikumar S., Corcoran B., Becker E. L. The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils. J Exp Med. 1976 May 1;143(5):1154–1169. doi: 10.1084/jem.143.5.1154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Walker J. R., James D. W., Smith M. J. Directed migration of circulating polymorphonuclear leucocytes in patients with rheumatoid arthritis: a defect in the plasma. Ann Rheum Dis. 1979 Jun;38(3):215–218. doi: 10.1136/ard.38.3.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weese J. L., McCoy J. L., Dean J. H., Ortaldo J. R., Burk K. R., Herberman R. B. Brief communication: technical modifications of the human agarose microdroplet leukocyte migration inhibition assay. J Immunol Methods. 1978;24(3-4):363–370. doi: 10.1016/0022-1759(78)90139-4. [DOI] [PubMed] [Google Scholar]
  23. Wright D. G., Kirkpatrick C. H., Gallin J. I. Effects of levamisole on normal and abnormal leukocyte locomotion. J Clin Invest. 1977 May;59(5):941–950. doi: 10.1172/JCI108716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zigmond S. H., Hirsch J. G. Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor. J Exp Med. 1973 Feb 1;137(2):387–410. doi: 10.1084/jem.137.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]

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