Differences in proliferation of the hematopoietic cell line TF-1 and cytokine production by peripheral blood leukocytes induced by 2 naturally occurring forms of human IL-3

Andrea Schweiger, Debra Stern, I. Carla Lohman, Mauro Baldini, Fernando Martinez, Marilyn Halonen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: A naturally occurring polymorphism in the coding region of the human IL3 gene leads to a change in amino acid residue 8 from proline to serine. Objective: We sought to determine whether the 2 different forms of IL-3 varied in function. These different forms are available as recombinant proteins (recombinant human IL-3/proline 8 [rhIL-3/P8] and recombinant human IL-3/serine 8 [rhIL-3/S8]). Methods: The erythroleukemic cell line TF-1 was incubated with varying concentrations of rhIL-3/P8 or rhIL-3/S8 to determine the capacity of each type of IL-3 to induce proliferation. Human leukocytes were primed with rhIL-3/P8 or rhIL-3/S8 for up to 24 hours and then stimulated with anti-IgE and assessed for leukotrienes (LTs), IL-4, and TNF-α. Results: Proliferation of TF-1 cells was induced by both forms of IL-3 at 48 and 72 hours but to a greater degree by rhIL-3/P8. In contrast, the mean fold increase over control values of LT and IL-4 production was higher after priming the cells with rhIL-3/S8 versus rhIL-3/P8. Additionally, TNF-α production was greater (and reached significance only) for rhIL-3/S8. This activity was independent of IgE and thus directly stimulated by IL-3. Studies with basophil-enriched and basophildepleted cell preparations revealed that LT production was evident only from the former and TNF-α only from the latter. Conclusion: We conclude that the 2 naturally occurring forms of human IL-3 have similar spectra of activities on cells with IL-3 receptors, but the 2 forms have reversed relative efficacies for promoting proliferation (rhIL-3/P8 > rhIL-3/S8) compared with priming or inducing mediator secretion (rhIL-3/S8 > rhIL-3/P8).

Original languageEnglish (US)
Pages (from-to)505-510
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume107
Issue number3
DOIs
StatePublished - 2001

Fingerprint

Interleukin-3
Leukocytes
Cytokines
Cell Line
Proline
Serine
Leukotrienes
Interleukin-4
Interleukin-3 Receptors
Basophils

Keywords

  • IL-3
  • IL-3 receptor
  • Leukotrienes
  • Polymorphism
  • Priming
  • Proliferation
  • TNF-α IgE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Differences in proliferation of the hematopoietic cell line TF-1 and cytokine production by peripheral blood leukocytes induced by 2 naturally occurring forms of human IL-3. / Schweiger, Andrea; Stern, Debra; Lohman, I. Carla; Baldini, Mauro; Martinez, Fernando; Halonen, Marilyn.

In: Journal of Allergy and Clinical Immunology, Vol. 107, No. 3, 2001, p. 505-510.

Research output: Contribution to journalArticle

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abstract = "Background: A naturally occurring polymorphism in the coding region of the human IL3 gene leads to a change in amino acid residue 8 from proline to serine. Objective: We sought to determine whether the 2 different forms of IL-3 varied in function. These different forms are available as recombinant proteins (recombinant human IL-3/proline 8 [rhIL-3/P8] and recombinant human IL-3/serine 8 [rhIL-3/S8]). Methods: The erythroleukemic cell line TF-1 was incubated with varying concentrations of rhIL-3/P8 or rhIL-3/S8 to determine the capacity of each type of IL-3 to induce proliferation. Human leukocytes were primed with rhIL-3/P8 or rhIL-3/S8 for up to 24 hours and then stimulated with anti-IgE and assessed for leukotrienes (LTs), IL-4, and TNF-α. Results: Proliferation of TF-1 cells was induced by both forms of IL-3 at 48 and 72 hours but to a greater degree by rhIL-3/P8. In contrast, the mean fold increase over control values of LT and IL-4 production was higher after priming the cells with rhIL-3/S8 versus rhIL-3/P8. Additionally, TNF-α production was greater (and reached significance only) for rhIL-3/S8. This activity was independent of IgE and thus directly stimulated by IL-3. Studies with basophil-enriched and basophildepleted cell preparations revealed that LT production was evident only from the former and TNF-α only from the latter. Conclusion: We conclude that the 2 naturally occurring forms of human IL-3 have similar spectra of activities on cells with IL-3 receptors, but the 2 forms have reversed relative efficacies for promoting proliferation (rhIL-3/P8 > rhIL-3/S8) compared with priming or inducing mediator secretion (rhIL-3/S8 > rhIL-3/P8).",
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T1 - Differences in proliferation of the hematopoietic cell line TF-1 and cytokine production by peripheral blood leukocytes induced by 2 naturally occurring forms of human IL-3

AU - Schweiger, Andrea

AU - Stern, Debra

AU - Lohman, I. Carla

AU - Baldini, Mauro

AU - Martinez, Fernando

AU - Halonen, Marilyn

PY - 2001

Y1 - 2001

N2 - Background: A naturally occurring polymorphism in the coding region of the human IL3 gene leads to a change in amino acid residue 8 from proline to serine. Objective: We sought to determine whether the 2 different forms of IL-3 varied in function. These different forms are available as recombinant proteins (recombinant human IL-3/proline 8 [rhIL-3/P8] and recombinant human IL-3/serine 8 [rhIL-3/S8]). Methods: The erythroleukemic cell line TF-1 was incubated with varying concentrations of rhIL-3/P8 or rhIL-3/S8 to determine the capacity of each type of IL-3 to induce proliferation. Human leukocytes were primed with rhIL-3/P8 or rhIL-3/S8 for up to 24 hours and then stimulated with anti-IgE and assessed for leukotrienes (LTs), IL-4, and TNF-α. Results: Proliferation of TF-1 cells was induced by both forms of IL-3 at 48 and 72 hours but to a greater degree by rhIL-3/P8. In contrast, the mean fold increase over control values of LT and IL-4 production was higher after priming the cells with rhIL-3/S8 versus rhIL-3/P8. Additionally, TNF-α production was greater (and reached significance only) for rhIL-3/S8. This activity was independent of IgE and thus directly stimulated by IL-3. Studies with basophil-enriched and basophildepleted cell preparations revealed that LT production was evident only from the former and TNF-α only from the latter. Conclusion: We conclude that the 2 naturally occurring forms of human IL-3 have similar spectra of activities on cells with IL-3 receptors, but the 2 forms have reversed relative efficacies for promoting proliferation (rhIL-3/P8 > rhIL-3/S8) compared with priming or inducing mediator secretion (rhIL-3/S8 > rhIL-3/P8).

AB - Background: A naturally occurring polymorphism in the coding region of the human IL3 gene leads to a change in amino acid residue 8 from proline to serine. Objective: We sought to determine whether the 2 different forms of IL-3 varied in function. These different forms are available as recombinant proteins (recombinant human IL-3/proline 8 [rhIL-3/P8] and recombinant human IL-3/serine 8 [rhIL-3/S8]). Methods: The erythroleukemic cell line TF-1 was incubated with varying concentrations of rhIL-3/P8 or rhIL-3/S8 to determine the capacity of each type of IL-3 to induce proliferation. Human leukocytes were primed with rhIL-3/P8 or rhIL-3/S8 for up to 24 hours and then stimulated with anti-IgE and assessed for leukotrienes (LTs), IL-4, and TNF-α. Results: Proliferation of TF-1 cells was induced by both forms of IL-3 at 48 and 72 hours but to a greater degree by rhIL-3/P8. In contrast, the mean fold increase over control values of LT and IL-4 production was higher after priming the cells with rhIL-3/S8 versus rhIL-3/P8. Additionally, TNF-α production was greater (and reached significance only) for rhIL-3/S8. This activity was independent of IgE and thus directly stimulated by IL-3. Studies with basophil-enriched and basophildepleted cell preparations revealed that LT production was evident only from the former and TNF-α only from the latter. Conclusion: We conclude that the 2 naturally occurring forms of human IL-3 have similar spectra of activities on cells with IL-3 receptors, but the 2 forms have reversed relative efficacies for promoting proliferation (rhIL-3/P8 > rhIL-3/S8) compared with priming or inducing mediator secretion (rhIL-3/S8 > rhIL-3/P8).

KW - IL-3

KW - IL-3 receptor

KW - Leukotrienes

KW - Polymorphism

KW - Priming

KW - Proliferation

KW - TNF-α IgE

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