Abstract
Formylated peptides are potent stimulants of polymorphonuclear neutrophilic leukyocyte (PMN) migration from species such as humans and rabbits. Interestingly, PMNs from dogs, cats, pigs and cows have been reported as refractory toN-formyl-1-methionyl-1-leucyl-1-phenylalanine (FMLP) and generally are believed not to express formylpeptide receptors. Formylpeptides are a major component of conditioned media fromE. coli cultures and believed to be a significant element in inflammatory responses elicited byE. coli. Our studies have found thatE. coli filtrate was a potent stimulant of dog PMN migration. Inhibition of migration toE. coli filtrates by the antagonistt-botyloxycarbonyl-1-methionyl-1-leucyl-1-phenylalanine (t-boc-MLP) demonstrated that the migration was mediated through the formylated peptide receptor. Migration in response to peptides with higher affinity for the formylpeptide receptor than FMLP was further evidence for these receptors on the dog PMN. PMNs from dogs migrated in response to FMLP at high concentrations (100μM); however, pretreatment with phorbol myristate acetate resulted in increased migration of dog PMNs in response to concentrations of FMLP as low as 1 pM. These results demonstrate that dog PMNs are responsive to formylpeptides and that these responses can be up-regulated by PMA. Thus PMNs from a species previously thought incapable of responding to formylpeptides can respond to formylpeptide analogs with high affinity for the receptor as well as be primed for enhanced migration to FMLP by PMA.
Similar content being viewed by others
References
Schiffmann, E., B. A. Corcoran, andS. M. Wahl, 1977.N-Formylmethionyl peptides as chemoattractants for leukocytes.Proc. Natl. Acad. Sci. U.S.A. 72:1059.
Marasco, W. A., S. H. Phan, H. E. Krutzsche, H. J. Showell, D. E. Feltner, R. Nairn, E. L. Becker, andP. A. Ward. 1984. Purification and identification of formyl-methionylleucyl-phenylalanine as the major peptide neutrophil chemotactic factor produced byE. coli.J. Immunol. 259:5430.
Showell, H. J., R. H. Freer, S. H. Zigmond, E. Schiffmann, S. Aswanikumar, B. Corcoran, andE. L. Becker. 1976. The structure-activity relations of synthetic peptides as chemotacic factors and inducers of lysosomal enzyme secretion for neutrophils.J. Exp. Med. 143:1154.
Williams, L. T., R. Snyderman, M. C. Pike, andR. J. Lefkowitz. 1977. Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes.Proc. Natl. Acad. Sci. U.S.A. 74:1204.
Zimmerli, W., B. Seligmann, andJ. Gallin. 1986. Exudation primes human and guinea pig neutrophils for subsequent responsiveness to the chemotactic peptideN-formylmethionyl-phenylalanine and increases complement component C3bi receptor expression.J. Clin Invest. 77:925.
Gallin, J. L., D. G. Wright, andE. Schiffmann. 1978. Role of secretory events in modulating human neutrophil chemotaxis.J. Clin Invest. 62:1364.
Aswanikumar, S., B. Corcoran, andE. Schiffmann. 1977. Demonstration of a receptor on rabbit neutrophils for chemotactic peptide.Biochem. Biophys. Res. Commun. 74:810.
Freer, R. J., A. R. Day, N. Muthukumaraswamy, D. Pinon, A. Wu, H. J. Showell, andE. L. Becker. 1982. Formyl peptide chemoattractants: A model of the receptor on rabbit neutrophils.Biochemistry 21:257.
Niedel, J., S. Wilkinson, andP. Cuatrecasas. 1979. Receptor-mediated uptake and degradation of125I-chemotactic peptide by human neutrophils.J. Biol. Chem. 254:10700.
Redl, H., P. J. Flynn, H. Lamche, S. Schiesser, S. Gunther, andD. E. Hammerschidt. 1983. Aggregation, chemotaxis, and chemiluminescence of canine granulocytes.Inflammation 7:67.
Stickle, J. E., D. G. Kwan, andC. W. Smith. 1985. Neutrophil function in the dog: Shape change and response to a synthetic tripeptide.Am. J. Vet. Res. 46:225.
Gray, G. D., K. A. Knight, R. D. Nelson, andM. J. Herron. 1982. Chemotactic requirements of bovine leukocytes.Am. J. Vet. Res. 43:757.
Chenoweth, D. E., T. A. Lane, F. G. Rowe, andT. E. Hugli. 1980. Quantitative comparisons of neutrophil chemotaxis in four animal species.Clin. Immunol. Jmmunopathol. 15:525.
Gray, G. D., G. M. Ohlmann, D. R. Morton, andR. G. Schaaub. 1986. Feline polymorphonuclear leukocytes respond chemotactically to leukotriene B4 and activated serum but not to F-Met-Leu-Phe.Agents Actions 18:401.
Cook, L. O., L. A. Boxer, J. M. Allen, J. A. Grief, andR. L. Baehner. 1978. In vitro functional capabilities of canine PMNs collected simultaneously by continuous-flow centrifugation and continuous-flow filtration leukopheresis.Am. J. Hematol. 4:225.
Falk, W., R. H. Goodwin, andE. J. Leonard, 1980. A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration.J. Immunol. Methods 33:239.
Fletcher, M. P., B. E. Seligmann, andJ. I. Gallin, 1982. Correlation of human neutrophil secretion, chemoattractant receptor mobilization, and enhanced functional capacity.J. Immunol. 128:941.
Munson, P. J., andD. Rodbard. 1980. Ligand: A versatile computerized approach for characterization of ligand binding systems.Anal. Biochem. 107:220.
Linnekin, D. M. 1988. Modulation of PMN responses to F-Met-Leu-Phe. PhD dissertation. Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Verghese, M. W., L. Charles, L. Jakoi, S. B. Dillon, andR. Synderman. 1987. Role of a guanine nucleotide reglulatory protein in the activation of phosphiolipase C by different chemoattractants.J. Immunol. 138:4374.
Estensen, R. C., H. R. Hill, P. G. Quie, N. Hogan, andN. D. Goldberg. 1973. Cyclic GMP and cell movement.Nature 245:458.
Fletcher M. P., andJ. I. Gallin. 1980. Degranulating stimuli increase the availability of receptors on human neutrophils for the chemoattractant f-Met-Leu-Phe.J. Immunol. 124:1585.
Fletcher, M. P., andJ. I. Gallin. 1983. Human neutrophils contain an intracellular pool of putative receptors for the chemoattractantN-formyl-methionyl-leucyl-phenylalanine.Blood 62:792.
Anderson, R., andJ. Niedel. 1984. Processing of the formyl peptide receptor by HL-60 Cells.J. Biol. Chem. 259:13309.
Jesaitis, A. J., J. R. Naemaur, R. G. Painter, L. E. Sklar, andC. G. Cochrane. 1982. Intracellular localization ofN-formyl chemotactic receptor and Mg-dependent ATPase in human granulocytes.Biochim. Biophys. Acta 719:556.
Hunter, T., andJ. A. Cooper. 1985. Protein-tyrosine kinases.Annu. Rev. Biochem. 54:897.
D. W. Goldman, J. Enkel, L. A. Gifford, D. E. Chenoweth, andJ. T. Rosenbaum. 1986. Lipopolysaccharide modulates receptors for leukotriene B4, C5a and formyl-methionyl-leucylphenylalanine on rabbit polymorphonuclear leukocytes.J. Immunol. 137:1971.
Fletcher, M. P. 1986. Modulation of the heterogeneous membrane potential response of neutrophils toN-formyl-methionyl-leucyl-phenylalanine (FMLP) by leukotriene B4: Evidence for cell recruitment.J. Immunol. 136:4213.
Gay, J. C., J. K. Beckman, A. R. Brash, J. A. Oates, andJ. N. Lukens. 1984. Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4.Blood 64:780.
Gay, J. C., J. K. Beckman, L. A. Zaboy, andJ. N. Lukens. 1986. Modulation of neutrophil oxidative responses to soluble stimuli by platelet-activating factor.Blood 67:931.
Ingraham, L. M., J. E. Lafuze, L. A. Boxer, andR. L. Baehner. 1987. In vitro and in vivo effects of treatment by platelet-activating factor onN-formyl-methionyl-leucyl-phenylalanine mediated responses of polymorphonuclear leucocytes.Br. J. Haematol 66:219.
Weishart, R. H., D. W. Golde, andJ. C. Gasson. 1986. Biosynthetic human GM-CSF modulates the number and affinity of neutrophil f-Met-Leu-Phe Receptors.J. Immunol. 137:3584.
Fletcher, M. P., andJ. C. Gasson. 1988. Priming of neutrophils by rhGM-CSF involves recruitment of a less responsive subpopulation.J. Immunol. 71:652.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Linnekin, D., Bowles, C.A., Murano, G. et al. Migration of dog polymorphonuclear neutrophilic leukocytes to formylated peptides. Inflammation 14, 691–703 (1990). https://doi.org/10.1007/BF00916372
Issue Date:
DOI: https://doi.org/10.1007/BF00916372