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Infection and Immunity, June 2001, p. 3933-3938, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3933-3938.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Normal Human Fibroblasts Express Pattern Recognition Receptors for Fungal (1right-arrow 3)-beta -D-Glucans

Panagiotis Kougias,1 Duo Wei,1 Peter J. Rice,2 Harry E. Ensley,3 John Kalbfleisch,4 David L. Williams,1,5,* and I. William Browder1,5

Departments of Surgery,1 Pharmacology,2 and Medical Education,4 James H. Quillen College of Medicine, Johnson City, Tennessee 37614; Department of Chemistry, Tulane University, New Orleans, Louisiana 701153; and James H. Quillen Veterans Affairs Medical Center, Mountain Home, Tennessee 376145

Received 11 January 2001/Returned for modification 7 February 2001/Accepted 27 February 2001

Fungal cell wall glucans nonspecifically stimulate various aspects of innate immunity. Glucans are thought to mediate their effects via interaction with membrane receptors on macrophages, neutrophils, and NK cells. There have been no reports of glucan receptors on nonimmune cells. We investigated the binding of a water-soluble glucan in primary cultures of normal human dermal fibroblasts (NHDF). Membranes from NHDF exhibited saturable binding with an apparent dissociation constant (KD) of 8.9 ± 1.9 µg of protein per ml and a maximum binding of 100 ± 8 resonance units. Competition studies demonstrated the presence of at least two glucan binding sites on NHDF. Glucan phosphate competed for all binding sites, with a KD of 5.6 µM (95% confidence interval [CI], 3.0 to 11 µM), while laminarin competed for 69% ± 6% of binding sites, with a KD of 3.7 µM (95% CI, 1.9 to 7.3 µM). Glucan (1 µg/ml) stimulated fibroblast NF-kappa B nuclear binding activity and interleukin 6 (IL-6) gene expression in a time-dependent manner. NF-kappa B was activated at 4, 8, and 12 h, while IL-6 mRNA levels were increased by 48% at 8 h. This is the first report of pattern recognition receptors for glucan on human fibroblasts and the first demonstration of glucan binding sites on cells other than leukocytes. It also provides the first evidence that glucans can directly modulate the functional activity of NHDF. These results provide new insights into the mechanisms by which the host recognizes and responds to fungal (1right-arrow3)-beta -D-glucans and suggests that the response to glucans may not be confined to cells of the immune system.

* Corresponding author. Mailing address: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, P.O. Box 70575, Johnson City, TN 37614-0575. Phone: (423) 439-6363. Fax: (423) 439-6259. E-mail: williamd{at}etsu.edu.

Infection and Immunity, June 2001, p. 3933-3938, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3933-3938.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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