Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1982 Apr;69(4):889–899. doi: 10.1172/JCI110528

Identification and partial characterization of an exercise-induced neutrophil chemotactic factor in bronchial asthma.

T H Lee, L Nagy, T Nagakura, M J Walport, A B Kay
PMCID: PMC370143  PMID: 7076852

Abstract

A heat-stable neutrophil chemotactic factor (NCF) has been identified in the serum of 13 atopic asthmatic subjects after treadmill exercise. Peak activity was detected at 10 min and returned to prechallenge values by 1 h. No NCF activity was detected in the sera of three nonasthmatic atopic or four normal nonatopic individuals performing the same task. NCF produced by exercise (NCFEX) had a similar time-course of release to NCF provoked by specific antigen (NCFAG). The appearance of circulating NCFEX and NCFAG closely paralleled the fall in peak expiratory flow rate/forced expiratory volume in 1 s (PEFR/FEV1). Histamine challenge in atopic asthmatics at concentrations giving a comparable change in PEFR/FEV1 to that evoked by exercise or inhaled antigen was not associated with the appearance of circulating NCF. In seven subjects NCFEX release was inhibited by prior administration of disodium cromoglycate. NCFEX and NCFAG eluted as single peaks of activity when applied separately to columns of Sephadex G-200, and both were an estimated 750,000 daltons. NCFEX and NCFAG also eluted as single peaks of activity, at between 0.15 and 0.30 M NaCl, following anion exchange chromatography on DEAE-Sephacel (pH 7.8). The isoelectric points of NCFEX and NCFAG were virtually identical (between pH 6.0 and 6.5) as determined by chromatofocusing on Polybuffer Exchanger 94. The activities of NCFEX and NCFAG were substantially reduced, in both a time- and dose-dependent fashion, after incubation with trypsin and chymotrypsin. Partially purified NCFEX and NCFAG promoted both stimulated random migration (chemokinesis) as well as directional migration (chemotaxis). These experiments indicate that NCFEX and NCFAG might be identical substances and raise the possibility that mediators by hypersensitivity are released during exercise-induced asthma in atopic subjects.

Full text

PDF
889

Selected References

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

  1. Allen T. W., Addington W., Rosendal T., Cugell D. W. Alveolar carbon dioxide and airway resistance in patients with postexercise bronchospasm. Am Rev Respir Dis. 1973 May;107(5):816–821. doi: 10.1164/arrd.1973.107.5.816. [DOI] [PubMed] [Google Scholar]
  2. Atkins P. C., Norman M. E., Zweiman B. Antigen-induced neutrophil chemotactic activity in man. Correlation with bronchospasm and inhibition by disodium cromoglycate. J Allergy Clin Immunol. 1978 Sep;62(3):149–155. doi: 10.1016/0091-6749(78)90099-4. [DOI] [PubMed] [Google Scholar]
  3. Atkins P. C., Norman M., Weiner H., Zweiman B. Release of neutrophil chemotactic activity during immediate hypersensitivity reactions in humans. Ann Intern Med. 1977 Apr;86(4):415–418. doi: 10.7326/0003-4819-86-4-415. [DOI] [PubMed] [Google Scholar]
  4. Atkins P., Green G. R., Zweiman B. Histologic studies of human skin test responses to ragweed, compound 48-80, and histamine. J Allergy Clin Immunol. 1973 May;51(5):263–273. doi: 10.1016/0091-6749(73)90128-0. [DOI] [PubMed] [Google Scholar]
  5. Brown M. J., Ind P. W., Barnes P. J., Jenner D. A., Dollery C. T. A sensitive and specific radiometric method for the measurement of plasma histamine in normal individuals. Anal Biochem. 1980 Nov 15;109(1):142–146. doi: 10.1016/0003-2697(80)90022-6. [DOI] [PubMed] [Google Scholar]
  6. DUNER H., PERNOW B. Histamine and leukocytes in blood during muscular work in man. Scand J Clin Lab Invest. 1958;10(4):394–396. doi: 10.3109/00365515809051243. [DOI] [PubMed] [Google Scholar]
  7. Deal E. C., Jr, McFadden E. R., Jr, Ingram R. H., Jr, Jaeger J. J. Hyperpnea and heat flux: initial reaction sequence in exercise-induced asthma. J Appl Physiol Respir Environ Exerc Physiol. 1979 Mar;46(3):476–483. doi: 10.1152/jappl.1979.46.3.476. [DOI] [PubMed] [Google Scholar]
  8. Deal E. C., Jr, McFadden E. R., Jr, Ingram R. H., Jr, Strauss R. H., Jaeger J. J. Role of respiratory heat exchange in production of exercise-induced asthma. J Appl Physiol Respir Environ Exerc Physiol. 1979 Mar;46(3):467–475. doi: 10.1152/jappl.1979.46.3.467. [DOI] [PubMed] [Google Scholar]
  9. Deal E. C., Jr, Wasserman S. I., Soter N. A., Ingram R. H., Jr, McFadden E. R., Jr Evaluation of role played by mediators of immediate hypersensitivity in exercise-induced asthma. J Clin Invest. 1980 Mar;65(3):659–665. doi: 10.1172/JCI109711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dolovich J., Hargreave F. E., Chalmers R., Shier K. J., Gauldie J., Bienenstock J. Late cutaneous allergic responses in isolated IgE-dependent reactions. J Allergy Clin Immunol. 1973 Jul;52(1):38–46. doi: 10.1016/0091-6749(73)90119-x. [DOI] [PubMed] [Google Scholar]
  11. Dolovich J., Little D. C. Correlates of skin test reactions to Bacillus subtilis enzyme preparations. J Allergy Clin Immunol. 1972 Jan;49(1):43–53. doi: 10.1016/0091-6749(72)90122-4. [DOI] [PubMed] [Google Scholar]
  12. Edmunds A. T., Tooley M., Godfrey S. The refractory period after exercise-induced asthma: its duration and relation to the severity of exercise. Am Rev Respir Dis. 1978 Feb;117(2):247–254. doi: 10.1164/arrd.1978.117.2.247. [DOI] [PubMed] [Google Scholar]
  13. Eosinophils and mediators of anaphylaxis. Histamine and imidazole acetic acid as chemotactic agents for human eosinophil leucocytes. Immunology. 1976 Nov;31(5):797–802. [PMC free article] [PubMed] [Google Scholar]
  14. Godfrey S., Silverman M., Anderson S. D. Problems of interpreting exercise-induced asthma. J Allergy Clin Immunol. 1973 Oct;52(4):199–209. doi: 10.1016/0091-6749(73)90058-4. [DOI] [PubMed] [Google Scholar]
  15. Harries M. G., Burge P. S., O'Brien I. M. Occupational type bronchial provocation tests: testing with soluble antigens by inhalation. Br J Ind Med. 1980 Aug;37(3):248–252. doi: 10.1136/oem.37.3.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Harries M. G., Burge P. S., O'Brien I., Cromwell O., Pepys J. Blood histamine levels after exercise testing. Clin Allergy. 1979 Sep;9(5):437–441. doi: 10.1111/j.1365-2222.1979.tb02506.x. [DOI] [PubMed] [Google Scholar]
  17. JONES R. S., BUSTON M. H., WHARTON M. J. The effect of exercise on ventilatory function in the child with asthma. Br J Dis Chest. 1962 Apr;56:78–86. doi: 10.1016/s0007-0971(62)80005-9. [DOI] [PubMed] [Google Scholar]
  18. Katz R. M., Whipp B. J., Heimlich E. M., Wasserman K. Exercise-induced bronchospasm, ventilation, and blood gases in asthmatic children. J Allergy. 1971 Mar;47(3):148–158. doi: 10.1016/s0091-6749(71)80293-2. [DOI] [PubMed] [Google Scholar]
  19. Kay A. B. Studies on eosinophil leucocyte migration. I. Eosinophil and neutrophil accumulation following antigen-antibody reactions in guinea-pig skin. Clin Exp Immunol. 1970 Jan;6(1):75–86. [PMC free article] [PubMed] [Google Scholar]
  20. Lewis R. A., Goetzl E. J., Wasserman S. I., Valone F. H., Rubin R. H., Austen K. F. The release of four mediators of immediate hypersensitivity from human leukemic basophils. J Immunol. 1975 Jan;114(1 Pt 1):87–92. [PubMed] [Google Scholar]
  21. Lugliani R., Whipp B. J., Seard C., Wasserman K. Effect of bilateral carotid-body resection on ventilatory control at rest and during exercise in man. N Engl J Med. 1971 Nov;285(20):1105–1111. doi: 10.1056/NEJM197111112852002. [DOI] [PubMed] [Google Scholar]
  22. Nagy L. The effect of disodium-chromoglykate on human serum neutrophil-chemotactic activity in antigen induced bronchospasm. Allerg Immunol (Leipz) 1981;27(1):48–52. [PubMed] [Google Scholar]
  23. Solley G. O., Gleich G. J., Jordon R. E., Schroeter A. L. The late phase of the immediate wheal and flare skin reaction. Its dependence upon IgE antibodies. J Clin Invest. 1976 Aug;58(2):408–420. doi: 10.1172/JCI108485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Soter N. A., Wasserman S. I., Austen K. F., McFadden E. R., Jr Release of mast-cell mediators and alterations in lung function in patients with cholinergic urticaria. N Engl J Med. 1980 Mar 13;302(11):604–608. doi: 10.1056/NEJM198003133021104. [DOI] [PubMed] [Google Scholar]
  25. Stearns D. R., McFadden E. R., Jr, Breslin F. J., Ingram R. H., Jr Reanalysis of the refractory period in exertional asthma. J Appl Physiol Respir Environ Exerc Physiol. 1981 Mar;50(3):503–508. doi: 10.1152/jappl.1981.50.3.503. [DOI] [PubMed] [Google Scholar]
  26. Strauss R. H., McFadden E. R., Jr, Ingram R. H., Jr, Deal E. C., Jr, Jaeger J. J. Influence of heat and humidity on the airway obstruction induced by exercise in asthma. J Clin Invest. 1978 Feb;61(2):433–440. doi: 10.1172/JCI108954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vassallo C. L., Gee J. B., Domm B. M. Exercise-induced asthma. Observations regarding hypocapnia and acidosis. Am Rev Respir Dis. 1972 Jan;105(1):42–49. doi: 10.1164/arrd.1972.105.1.42. [DOI] [PubMed] [Google Scholar]
  28. Wasserman S. I., Soter N. A., Center D. M., Austen K. F. Cold urticaria. Recognition and characterization of a neutrophil chemotactic factor which appears in serum during experimental cold challenge. J Clin Invest. 1977 Jul;60(1):189–196. doi: 10.1172/JCI108756. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES