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. 1978 Mar;61(3):770–780. doi: 10.1172/JCI108991

Production of a Low Molecular Weight Eosinophil Polymorphonuclear Leukocyte Chemotactic Factor by Anaplastic Squamous Cell Carcinomas of Human Lung

Edward J Goetzl 1,2,3,4, Armen H Tashjian Jr 1,2,3,4, Robert H Rubin 1,2,3,4, K Frank Austen 1,2,3,4
PMCID: PMC372592  PMID: 641154

Abstract

A peptide of approximately 300-400 daltons exhibiting in vitro chemotactic activity for human polymorphonuclear (PMN) leukocytes, with a preference for the eosinophil series, was isolated from extracts of anaplastic lung carcinomas of the large squamous cell type obtained from three patients with marked peripheral blood hypereosinophilia and eosinophilic infiltration of the tumors and surrounding normal pulmonary tissues. This chemotactic factor was termed ECF-LSC (eosinophil chemotactic factor of lung squamous cell carcinoma). ECF-LSC appeared in the urine of two of the patients in increasing quantities late in the course of their disease and was also elaborated by long-term cultures of dispersed tumor cells from the same two patients. Three anaplastic large cell bronchogenic carcinomas which were not associated with tumor tissue or peripheral blood eosinophilia, a bronchogenic adenocarcinoma from a patient with only peripheral eosinophilia, and a renal cell carcinoma metastatic to the lungs and associated with transient pleural tissue and fluid eosinophilia were all devoid of ECF-LSC. ECF-LSC from tumor tissue extracts, urine, and tumor cell culture medium was comparable to the mast cell-associated tetrapeptides of the eosinophil chemotactic factor of anaphylaxis (ECF-A) in size, but eluted from Dowex-1 at pH 5.0-3.5 in contrast to the more acidic ECF-A tetrapeptides which eluted at pH 3.2-2.2 ECF-LSC, like the tetrapeptides of ECF-A, had a secondary chemotactic activity for neutrophil PMN leukocytes, but not mononuclear leukocytes, and deactivated both eosinophil and neutrophil PMN leukocytes so that they would not respond to a subsequent in vitro chemotactic stimulus. Eosinophils from the two patients with urinary excretion of ECF-LSC and the highest concentrations in tumor extracts were hyporesponsive in vitro to homologous and heterologous chemotactic stimuli, suggesting that ECF-LSC had deactivated the eosinophils in vivo.

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Selected References

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  1. BOYDEN S. The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J Exp Med. 1962 Mar 1;115:453–466. doi: 10.1084/jem.115.3.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beaven M. A., Jacobsen S., Horáková Z. Modification of the enzymatic isotopic assay of histamine and its application to measurement of histamine in tissues, serum and urine. Clin Chim Acta. 1972 Mar;37:91–103. doi: 10.1016/0009-8981(72)90419-6. [DOI] [PubMed] [Google Scholar]
  3. Becker E. L. The relationship of the chemotactic behavior of the complement-derived factors, C3a, C5a, and C567, and a bacterial chemotactic factor to their ability to activate the proesterase 1 of rabbit polymorphonuclear leukocytes. J Exp Med. 1972 Feb 1;135(2):376–387. doi: 10.1084/jem.135.2.376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berke R., Wagshol L. E., Sullivan G. Incidence of intestinal parasites in Vietnam veterans. Eosinophilia a guide to diagnosis. Am J Gastroenterol. 1972 Jan;57(1):63–67. [PubMed] [Google Scholar]
  5. Fusco F. D., Rosen S. W. Gonadotropin-producing anaplastic large-cell carcinomas of the lung. N Engl J Med. 1966 Sep 8;275(10):507–515. doi: 10.1056/NEJM196609082751001. [DOI] [PubMed] [Google Scholar]
  6. Gewirtz G., Yalow R. S. Ectopic ACTH production in carcinoma of the lung. J Clin Invest. 1974 Apr;53(4):1022–1032. doi: 10.1172/JCI107639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goetzl E. J., Austen K. F. A neutrophil-immobilizing factor derived from human leukocytes. I. Generation and partial characterization. J Exp Med. 1972 Dec 1;136(6):1564–1580. doi: 10.1084/jem.136.6.1564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goetzl E. J., Austen K. F. Purification and synthesis of eosinophilotactic tetrapeptides of human lung tissue: identification as eosinophil chemotactic factor of anaphylaxis. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4123–4127. doi: 10.1073/pnas.72.10.4123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goetzl E. J. Modulation of human neutrophil polymorphonuclear leucocyte migration by human plasma alpha-globulin inhibitors and synthetic esterase inhibitors. Immunology. 1975 Jul;29(1):163–174. [PMC free article] [PubMed] [Google Scholar]
  10. Goetzl E. J. Plasma and cell-derived inhibitors of human neutrophil chemotaxis. Ann N Y Acad Sci. 1975 Jun 13;256:210–221. doi: 10.1111/j.1749-6632.1975.tb36048.x. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Goetzl E. J., Woods J. M., Gorman R. R. Stimulation of human eosinophil and neutrophil polymorphonuclear leukocyte chemotaxis and random migration by 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid. J Clin Invest. 1977 Jan;59(1):179–183. doi: 10.1172/JCI108617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hardy W. R., Anderson R. E. The hypereosinophilic syndromes. Ann Intern Med. 1968 Jun;68(6):1220–1229. doi: 10.7326/0003-4819-68-6-1220. [DOI] [PubMed] [Google Scholar]
  14. IVY H. K. Renal sodium loss and bronchogenic carcinoma. Associated autonomic neuropathy. Arch Intern Med. 1961 Jul;108:47–55. doi: 10.1001/archinte.1961.03620070049007. [DOI] [PubMed] [Google Scholar]
  15. Kaplan A. P., Kay A. B., Austen K. F. A prealbumin activator of prekallikrein. 3. Appearance of chemotactic activity for human neutrophils by the conversion of human prekallikrein to kallikrein. J Exp Med. 1972 Jan;135(1):81–97. doi: 10.1084/jem.135.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kay A. B., Austen K. F. The IgE-mediated release of an eosinophil leukocyte chemotactic factor from human lung. J Immunol. 1971 Sep;107(3):899–902. [PubMed] [Google Scholar]
  17. Kay A. B., Stechschulte D. J., Austen K. F. An eosinophil leukocyte chemotactic factor of anaphylaxis. J Exp Med. 1971 Mar 1;133(3):602–619. doi: 10.1084/jem.133.3.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lafferty F. W. Pseudohyperparathyroidism. Medicine (Baltimore) 1966 May;45(3):247–260. doi: 10.1097/00005792-196605000-00004. [DOI] [PubMed] [Google Scholar]
  19. Liddle G. W., Nicholson W. E., Island D. P., Orth D. N., Abe K., Lowder S. C. Clinical and laboratory studies of ectopic humoral syndromes. Recent Prog Horm Res. 1969;25:283–314. doi: 10.1016/b978-0-12-571125-8.50009-0. [DOI] [PubMed] [Google Scholar]
  20. Muggia F. M., Ghossein N. A., Wohl H. Eosinophilia following radiation therapy. Oncology. 1973;27(2):118–127. doi: 10.1159/000224727. [DOI] [PubMed] [Google Scholar]
  21. Tashjian A. H., Jr, Weintraub B. D., Barowsky N. J., Rabson A. S., Rosen S. W. Subunits of human chorionic gonadotropin: unbalanced synthesis and secretion by clonal cell strains derived from a bronchogenic carcinoma. Proc Natl Acad Sci U S A. 1973 May;70(5):1419–1422. doi: 10.1073/pnas.70.5.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wasserman S. I., Goetzl E. J., Austen K. F. Preformed eosinophil chemotactic factor of anaphylaxis (ECF-A). J Immunol. 1974 Jan;112(1):351–358. [PubMed] [Google Scholar]
  23. Wasserman S. I., Goetzl E. J., Ellman L., Austen K. F. Tumor-associated eosinophilotactic factor. N Engl J Med. 1974 Feb 21;290(8):420–424. doi: 10.1056/NEJM197402212900802. [DOI] [PubMed] [Google Scholar]
  24. Wasserman S. I., Whitmer D., Geotzl E. J., Austen K. F. Chemotactic deactivation of human eosinophils by the eosinophil chemotactic factor of anaphylaxis (38527). Proc Soc Exp Biol Med. 1975 Jan;148(1):301–306. doi: 10.3181/00379727-148-38527. [DOI] [PubMed] [Google Scholar]

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