Get access

Lung epithelial H292 cells induce differentiation of immature human HMC-1 mast cells by interleukin-6 and stem cell factor

Authors

  • Pompen,

    1. *1 Department of Pulmonology, 2 Clinical and Laboratory Immunology Unit, 3 Department of Pathology, Academic Medical Center, University of Amsterdam, §4 Laboratory for Experimental and Clinical Immunology, CLB Sanquin Blood Supply Foundation, Amsterdam, The Netherlands
    Search for more papers by this author
  • * Smids,

    1. *1 Department of Pulmonology, 2 Clinical and Laboratory Immunology Unit, 3 Department of Pathology, Academic Medical Center, University of Amsterdam, §4 Laboratory for Experimental and Clinical Immunology, CLB Sanquin Blood Supply Foundation, Amsterdam, The Netherlands
    Search for more papers by this author
  • * Dingemans,

    1. *1 Department of Pulmonology, 2 Clinical and Laboratory Immunology Unit, 3 Department of Pathology, Academic Medical Center, University of Amsterdam, §4 Laboratory for Experimental and Clinical Immunology, CLB Sanquin Blood Supply Foundation, Amsterdam, The Netherlands
    Search for more papers by this author
  • Jansen,

    1. *1 Department of Pulmonology, 2 Clinical and Laboratory Immunology Unit, 3 Department of Pathology, Academic Medical Center, University of Amsterdam, §4 Laboratory for Experimental and Clinical Immunology, CLB Sanquin Blood Supply Foundation, Amsterdam, The Netherlands
    Search for more papers by this author
  • * Out,

    1. *1 Department of Pulmonology, 2 Clinical and Laboratory Immunology Unit, 3 Department of Pathology, Academic Medical Center, University of Amsterdam, §4 Laboratory for Experimental and Clinical Immunology, CLB Sanquin Blood Supply Foundation, Amsterdam, The Netherlands
    Search for more papers by this author
  • and * Lutter

    1. *1 Department of Pulmonology, 2 Clinical and Laboratory Immunology Unit, 3 Department of Pathology, Academic Medical Center, University of Amsterdam, §4 Laboratory for Experimental and Clinical Immunology, CLB Sanquin Blood Supply Foundation, Amsterdam, The Netherlands
    Search for more papers by this author

Lutter Academic Medical Center, Department of Pulmonology/Clinical and Laboratory Immunology Unit, Room G1–140, PO Box 22700, 1100 DE Amsterdam, The Netherlands.

Abstract

Background

Immature mast cells migrate into tissues where they differentiate into mature mast cells under the influence of local factors. In the airways of asthmatics increased numbers of chronically activated mast cells are located nearby the airway epithelium.

Objective

The aim of this study was to evaluate whether and, if so, which products released by epithelial cells may affect mast cell proliferation and differentiation.

Methods

We performed in vitro studies using the human lung mucoepidermoid carcinoma-derived H292 cell line and the immature human mast cell line, HMC-1. Proliferation was assessed by 3H-thymidine incorporation. Differentiation of HMC-1 cells was inferred from tryptase production.

Results

Exposure of HMC-1 cells to medium conditioned for 48 h by H292 cells resulted in a reduction of proliferation with 65 ± 4.9% (mean ± sem, n = 9) at day 5. Culturing HMC-1 cells for 8 days in the presence of H292-conditioned medium resulted in morphological changes indicative of differentiation, and in a 3.0 ± 0.4-fold increase of tryptase production (P = 0.0039, n = 9). Conditioned medium from H292 cells that were stimulated by LPS also inhibited HMC-1 proliferation. Inhibitory antibodies against two mediators from H292 cells, interleukin-6 (IL-6) and stem cell factor (SCF), abolished the increase in HMC-1 tryptase production induced by H292-conditioned medium. Recombinant human (rh) IL-6, but not rhSCF, reduced HMC-1 proliferation with 44% and 13% at day 3 and 5, respectively. Surprisingly, rhIL-6 did not increase HMC-1 tryptase production significantly whereas incubation with rhSCF did (1.5 ± 0.1-fold, P = 0.002, n = 10) although the increase was less than observed for conditioned medium.

Conclusion

Epithelial-derived IL-6 and SCF are implicated in differentiation of HMC-1 cells but additional factors are not excluded. As activated primary bronchial epithelial cells also express IL-6 and SCF, it should be considered that these cells are involved in mast cell differentiation within the airways, particularly in diseases where epithelial cells are activated, such as asthma.

Get access to the full text of this article

Ancillary