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Red Blood Cells Stimulate Human Lung Fibroblasts to Secrete Interleukin-8

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Abstract

Following lung injury, red blood cells (RBC) may interact with extracellular matrix (ECM). Fibroblasts, the resident cell in the ECM, have the capacity to produce and secrete a variety of mediators including interleukin-8 (IL-8). In the present study we hypothesized that RBC, or soluble factors released from them, may stimulate IL-8 production by fibroblasts. Fibroblasts were cultured in a three-dimensional collagen gel culture system in the presence or absence of RBC or conditioned medium from RBC (RBC-CM). IL-8 release from fibroblasts was significantly increased when cultured with RBC or RBC-CM and both tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) further stimulated this IL-8 secretion. The enhanced production of IL-8 within fibroblasts was accompanied by increased IL-8 mRNA expression. To evaluate whether RBC-fibroblast interaction may lead to recruitment of neutrophils, a functional migration assay was performed. RBC and RBC-CM, in the presence of IL-1β and TNF-α, increased the transmigration of neutrophils. Our results indicate that RBC, when interacting with ECM, may participate in the recruitment of inflammatory cells by stimulating fibroblasts to secrete IL-8. This might be an important mechanism regulating tissue repair after injury.

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Authors and Affiliations

  1. Department of Medicine, Division of Respiratory Medicine, Karolinska Hospital, Stockholm, Sweden

    K. Fredriksson & J. Lundahl

  2. Karolinska Institutet, National Institute for Environmental Medicine, Stockholm, Sweden

    L. Palmberg

  3. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska

    D. J. Romberger, X. D. Liu, S. I. Rennard & C. M. Skold

Authors
  1. K. Fredriksson
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  2. J. Lundahl
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  3. L. Palmberg
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  4. D. J. Romberger
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  5. X. D. Liu
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  6. S. I. Rennard
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  7. C. M. Skold
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Correspondence to K. Fredriksson.

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Fredriksson, K., Lundahl, J., Palmberg, L. et al. Red Blood Cells Stimulate Human Lung Fibroblasts to Secrete Interleukin-8. Inflammation 27, 71–78 (2003). https://doi.org/10.1023/A:1023274532456

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