The Journal of Immunology, Vol 156, Issue 5 1946-1953, Copyright © 1996 by American Association of Immunologists

ARTICLES

Identification of an N-terminally truncated form of the chemokine RANTES and granulocyte-macrophage colony-stimulating factor as major eosinophil attractants released by cytokine-stimulated dermal fibroblasts

N Noso, M Sticherling, J Bartels, AI Mallet, E Christophers and JM Schroder
Department of Dermatology, University of Kiel, Federal Republic of Germany.

Eosinophil (Eo) granule proteins and, rarely, intact Eos represent a characteristic histopathologic feature of the dermal part of affected tissue in atopic dermatitis and some allergic reactions. Dermal fibroblasts are a rich source of cytokines and inflammatory mediators; therefore, we have investigated whether these cells release Eo chemoattractants when stimulated with different stimuli. Eo-chemotactic activity was detected after stimulation of cells with TNF-alpha and IL- 1, but not when phorbol ester, PHA, or medium alone was used. Biochemical characterization of Eo-chemotactic activity in supernatants of NF-alpha-stimulated cells revealed both heparin-binding and nonbinding activity. HPLC purification with subsequent N-terminal sequencing and mass spectrometric analysis showed that the heparin- binding Eo-chemotactic peak corresponded to the chemokine [Tyr- RANTES]66 that also contained [Ser-RANTES]68 as contaminant, whereas the nonheparin-binding activity was identified as granulocyte- macrophage CSF (GM-CSF) by the use of neutralizing Abs. [Tyr-RANTES]66 was found to show identical behavior in the chemotaxis assay system with respect to potency and efficacy as natural [Ser-RANTES]68. These findings support the hypothesis that dermal fibroblasts can play an important role in the recruitment of Eo by release of the chemokine RANTES together with GM-CSF.

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