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. 1979 Mar 1;80(3):564–572. doi: 10.1083/jcb.80.3.564

Selective neutrophil desensitization to chemotactic factors

PMCID: PMC2110355  PMID: 457760

Abstract

In the presence of extracellular calcium and magnesium, a series of chemotactic oligopeptides and C5a caused aggregation of human polymorphonuclear neutrophils (PMNs). This cellular response developed rapidly and began to reverse 2 min after exposure to the chemotactin. In the absence of the bivalent cations, none of the chemotactins stimulated the aggregation response. If cells were first exposed to a chemotactin and then treated with calcium and magnesium, aggregation was detected only after addition of the cations, and the magnitude of the response fell sharply as the interval between the addition of chemotactin and addition of cations was lengthened: when this interval exceeded 2 min, aggregation was barely detectable. This loss of reactivity persisted even when cells were re-exposed to fresh chemotactic factor and washed between the first and second exposures. In all instances, however, loss of cellular reactivity was highly selective: cells preincubated with any chemotactic oligopeptide were hyporesponsive to subsequent stimulation with an oligopeptide but remained fully responsive to C5a; cells preincubated with C5A were hyporesponsive to C5a but retained their responsitivity to the oligopeptides. Because this selectivity parallels the known specificities of these chemotactic factors for their receptors in or on the neutrophil, desensitization may reflect functional loss of receptors after stimulation. Alternatively, this selectivity may indicate that morphologically identical neutrophils contain subpopulations of cells with varying reactivities to receptor-bound chemotactic factors. In either event, desensitization may be useful in functionally defining chemotactic factors and their respective receptors. The rapidity of development of desensitization suggests that it may operate to limit or moderate various in vitro and in vivo neutrophil responses to chemotactic factors.

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Selected References

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  1. Aswanikumar S., Corcoran B., Schiffmann E., Day A. R., Freer R. J., Showell H. J., Becker E. L. Demonstration of a receptor on rabbit neutrophils for chemotactic peptides. Biochem Biophys Res Commun. 1977 Jan 24;74(2):810–817. doi: 10.1016/0006-291x(77)90375-8. [DOI] [PubMed] [Google Scholar]
  2. Aswanikumar S., Schiffmann E., Corcoran B. A., Wahl S. M. Role of a peptidase in phagocyte chemotaxis. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2439–2442. doi: 10.1073/pnas.73.7.2439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baxter J. H., Adamik R. Control of histamine release: effects of various conditions on rate of release and rate of cell desensitization. J Immunol. 1975 Mar;114(3):1034–1041. [PubMed] [Google Scholar]
  4. Boucek M. M., Snyderman R. Calcium influx requirement for human neutrophil chemotaxis: inhibition by lanthanum chloride. Science. 1976 Sep 3;193(4256):905–907. doi: 10.1126/science.948752. [DOI] [PubMed] [Google Scholar]
  5. Craddock P. R., Hammerschmidt D., White J. G., Dalmosso A. P., Jacob H. S. Complement (C5-a)-induced granulocyte aggregation in vitro. A possible mechanism of complement-mediated leukostasis and leukopenia. J Clin Invest. 1977 Jul;60(1):260–264. doi: 10.1172/JCI108763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goetzl E. J., Austen K. F. Structural determinants of the eosinophil: chemotactic activity of the acidic tetrapeptides of eosinophil chemotactic factor of anaphylaxis. J Exp Med. 1976 Dec 1;144(6):1424–1437. doi: 10.1084/jem.144.6.1424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goldstein I. M., Hoffstein S. T., Weissmann G. Influence of divalent cations upon complement-mediated enzyme release from human polymorphonuclear leukocytes. J Immunol. 1975 Sep;115(3):665–670. [PubMed] [Google Scholar]
  8. Goldstein I. M., Horn J. K., Kaplan H. B., Weissmann G. Calcium-induced lysozyme secretion from human polymorphonuclear leukocytes. Biochem Biophys Res Commun. 1974 Sep 23;60(2):807–812. doi: 10.1016/0006-291x(74)90312-x. [DOI] [PubMed] [Google Scholar]
  9. Henson P. M. Membrane receptors on neutrophils. Immunol Commun. 1976;5(9):757–774. doi: 10.3109/08820137609047618. [DOI] [PubMed] [Google Scholar]
  10. Mickenberg I. D., Snyderman R., Root R. K., Mergenhagen S. E., Wolff S. M. Immune fever in the rabbit: responses of the hematologic and complement systems. J Immunol. 1971 Nov;107(5):1457–1465. [PubMed] [Google Scholar]
  11. Naccache P. H., Showell H. J., Becker E. L., Sha'afi R. I. Changes in ionic movements across rabbit polymorphonuclear leukocyte membranes during lysosomal enzyme release. Possible ionic basis for lysosomal enzyme release. J Cell Biol. 1977 Dec;75(3):635–649. doi: 10.1083/jcb.75.3.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Naccache P. H., Showell H. J., Becker E. L., Sha'afi R. I. Transport of sodium, potassium, and calcium across rabbit polymorphonuclear leukocyte membranes. Effect of chemotactic factor. J Cell Biol. 1977 May;73(2):428–444. doi: 10.1083/jcb.73.2.428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. O'Flaherty J. T., Kreutzer D. L., Showell H. J., Ward P. A. Influence of inhibitors of cellular function on chemotactic factor-induced neutrophil aggregation. J Immunol. 1977 Nov;119(5):1751–1756. [PubMed] [Google Scholar]
  14. O'Flaherty J. T., Kreutzer D. L., Ward P. A. Chemotactic factor influences on the aggregation, swelling, and foreign surface adhesiveness of human leukocytes. Am J Pathol. 1978 Mar;90(3):537–550. [PMC free article] [PubMed] [Google Scholar]
  15. O'Flaherty J. T., Showell H. J., Kreutzer D. L., Ward P. A., Becker E. L. Inhibition of in vivo and in vitro neutrophil responses to chemotactic factors by a competitive antagonist. J Immunol. 1978 Apr;120(4):1326–1332. [PubMed] [Google Scholar]
  16. O'Flaherty J. T., Showell H. J., Ward P. A. Influence of calcium, magnesium, lanthanum and A23187 on the aggregation of polymorphonuclear neutrophils. Immunol Commun. 1978;7(5):495–502. doi: 10.3109/08820137809025480. [DOI] [PubMed] [Google Scholar]
  17. O'Flaherty J. T., Showell H. J., Ward P. A. Influence of extracellular Ca2+ and Mg2+ on chemotactic factor-induced neutrophil aggregation. Inflammation. 1977 Dec;2(4):265–276. doi: 10.1007/BF00921006. [DOI] [PubMed] [Google Scholar]
  18. O'Flaherty J. T., Showell H. J., Ward P. A. Neutropenia induced by systemic infusion of chemotactic factors. J Immunol. 1977 May;118(5):1586–1589. [PubMed] [Google Scholar]
  19. 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]
  20. Van Epps D. E., Bankhurst A. D., Williams R. C., Jr Casein-mediated neutrophil chemotaxis: a parallel between surface binding and chemotaxis. Inflammation. 1977 Jun;2(2):115–123. doi: 10.1007/BF00918673. [DOI] [PubMed] [Google Scholar]
  21. Ward P. A., Becker E. L. The deactivation of rabbit neutrophils by chemotactic factor and the nature of the activatable esterase. J Exp Med. 1968 Apr 1;127(4):693–709. doi: 10.1084/jem.127.4.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Williams L. T., Snyderman R., Pike M. C., Lefkowitz R. J. Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1204–1208. doi: 10.1073/pnas.74.3.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]

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