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. 1988 Nov;41(11):1163–1167. doi: 10.1136/jcp.41.11.1163

Leukotriene B4 synthesis and neutrophil chemotaxis in chronic granulocytic leukaemia.

I A Reilly 1, H R Knapp 1, G A Fitzgerald 1
PMCID: PMC1141723  PMID: 2850300

Abstract

A sensitive gas chromatography-mass spectrometric method was used to measure the generation in whole blood of leukotriene B4 (LTB4), a potent stimulator of neutrophil chemotaxis, in eight patients with chronic granulocytic leukaemia (CGL) and 12 healthy controls. LTB4 was detectable in unstimulated samples from all the patients (mean 194 (70 SEM) pg/ml), and the capacity for LTB4 production after stimulation with calcium ionophore (A23187) was similar in patients (32.1 (11) ng/10(6) leucocytes) and controls (38.1 (4) ng/10(6) leucocytes). In response to stimuli which induce neutrophil activation, LTB4 production was significantly greater in the patients than in controls: 35.6 (13) v 13.0 (3) ng/ml, p less than 0.05 (f-met-leu-phe); and 42.4 (16) v 14.7 (4) ng/ml, p less than 0.02 (opsonised zymosan). Anti-IgE stimulated considerably more LTB4 production in patients with CGL than in controls (3.86 (1.6) v 0.83 (0.43) ng/ml; p less than 0.005) and this correlated significantly (p less than 0.05) with the basophil count. Neutrophil chemotaxis to LTB4, however, was significantly impaired in the patients with CGL even at the highest concentration of LTB4 (10(-5) M). Chemotaxis to f-met-leu-phe, phagocytosis, and bacterial killing were normal. Thus although LTB4 synthesis is normal or even enhanced in patients with CGL, specific defects in LTB4-mediated responses may contribute to neutrophil dysfunction in this disease.

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Selected References

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

  1. Anklesaria P. N., Advani S. H., Bhisey A. N. Defective chemotaxis and adherence in granulocytes from chronic myeloid leukemia (CML) patients. Leuk Res. 1985;9(5):641–648. doi: 10.1016/0145-2126(85)90146-8. [DOI] [PubMed] [Google Scholar]
  2. Baker M. A., Kanani A., Hindenburg A., Taub R. N. Changes in the granulocyte membrane following chemotherapy for chronic myelogenous leukaemia. Br J Haematol. 1986 Mar;62(3):431–438. doi: 10.1111/j.1365-2141.1986.tb02954.x. [DOI] [PubMed] [Google Scholar]
  3. Baud L., Goldman D. W., Koo C. H., Marotti T., Harvey J. P., Goetzl E. J. Molecular and cellular diversity of the polymorphonuclear leukocyte receptors for leukotrienes. Adv Prostaglandin Thromboxane Leukot Res. 1987;17A:163–166. [PubMed] [Google Scholar]
  4. Benjamin C. W., Rupple P. L., Gorman R. R. Appearance of specific leukotriene B4 binding sites in myeloid differentiated HL-60 cells. J Biol Chem. 1985 Nov 15;260(26):14208–14213. [PubMed] [Google Scholar]
  5. Chenoweth D. E., Rowe J. G., Hugli T. E. A modified method for chemotaxis under agarose. J Immunol Methods. 1979;25(4):337–353. doi: 10.1016/0022-1759(79)90026-7. [DOI] [PubMed] [Google Scholar]
  6. El-Maalem H., Fletcher J. Defective neutrophil function in chronic granulocytic leukaemia. Br J Haematol. 1976 Sep;34(1):95–103. doi: 10.1111/j.1365-2141.1976.tb00178.x. [DOI] [PubMed] [Google Scholar]
  7. El-Maallem H., Fletcher J. Defective hydrogen peroxide production in chronic granulocytic leukaemia neutrophils. Br J Haematol. 1979 Jan;41(1):49–55. doi: 10.1111/j.1365-2141.1979.tb03680.x. [DOI] [PubMed] [Google Scholar]
  8. Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
  9. Glasser L., Fiederlein R. L. Functional differentiation of normal human neutrophils. Blood. 1987 Mar;69(3):937–944. [PubMed] [Google Scholar]
  10. Goldman D. W., Goetzl E. J. Heterogeneity of human polymorphonuclear leukocyte receptors for leukotriene B4. Identification of a subset of high affinity receptors that transduce the chemotactic response. J Exp Med. 1984 Apr 1;159(4):1027–1041. doi: 10.1084/jem.159.4.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kreisle R. A., Parker C. W. Specific binding of leukotriene B4 to a receptor on human polymorphonuclear leukocytes. J Exp Med. 1983 Feb 1;157(2):628–641. doi: 10.1084/jem.157.2.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lewis R. A., Austen K. F. The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology. J Clin Invest. 1984 Apr;73(4):889–897. doi: 10.1172/JCI111312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. O'Flaherty J. T., Wykle R. L., Lees C. J., Shewmake T., McCall C. E., Thomas M. J. Neutrophil-degranulating action of 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid and 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine. Comparison with other degranulating agents. Am J Pathol. 1981 Dec;105(3):264–269. [PMC free article] [PubMed] [Google Scholar]
  14. Palmblad J., Malmsten C. L., Udén A. M., Rådmark O., Engstedt L., Samuelsson B. Leukotriene B4 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence. Blood. 1981 Sep;58(3):658–661. [PubMed] [Google Scholar]
  15. Sumimoto H., Takeshige K., Minakami S. Superoxide production of human polymorphonuclear leukocytes stimulated by leukotriene B4. Biochim Biophys Acta. 1984 Apr 16;803(4):271–277. doi: 10.1016/0167-4889(84)90117-4. [DOI] [PubMed] [Google Scholar]
  16. Takayama H., Okuma M., Kanaji K., Sugiyama T., Sensaki S., Uchino H. Altered arachidonate metabolism by leukocytes and platelets in myeloproliferative disorders. Prostaglandins Leukot Med. 1983 Nov;12(3):261–272. doi: 10.1016/0262-1746(83)90004-5. [DOI] [PubMed] [Google Scholar]
  17. Taub R. N., Baker M. A., Madyastha K. R. Masking of neutrophil surface lectin-binding sites in chronic myelogenous leukemia (CML). Blood. 1980 Feb;55(2):294–298. [PubMed] [Google Scholar]
  18. Williams J. D., Czop J. K., Austen K. F. Release of leukotrienes by human monocytes on stimulation of their phagocytic receptor for particulate activators. J Immunol. 1984 Jun;132(6):3034–3040. [PubMed] [Google Scholar]

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