Am. J. Respir. Crit. Care Med., Volume 158, Number 3, September 1998, 769-777

Changes in CD11b and L-selectin Expression on Eosinophils Are Mediated by Human Lung Fibroblasts In Vitro

FOKJE M. SPOELSTRA, HESSEL HOVENGA, JACOBIEN A. NOORDHOEK, DIRKJE S. POSTMA, and HENK F. KAUFFMAN

Departments of Allergology and Pulmonology, University Hospital Groningen, Groningen, The Netherlands

Eosinophilic airway infiltration is a central feature in asthma. Eosinophils recovered from bronchoalveolar fluid show an activated phenotype, e.g., increased CD11b and decreased L-selectin expression. We investigated whether lung fibroblasts are able to activate eosinophils in vitro, and if so, which activating factor is most important. CD11b and L-selectin expression of isolated peripheral blood eosinophils were measured by flow cytometry after coculture with normal lung fibroblasts or their conditioned medium. We found that eosinophil CD11b expression increased (154% and 210%, p < 0.05) and L-selectin expression decreased (59% and 35.5%, p < 0.05) on eosinophils compared with baseline (100%) after 4 and 24 h of coculture with interleukin-1-beta (IL-1)-stimulated fibroblasts, respectively. Conditioned medium of stimulated fibroblasts also increased CD11b expression, but to a smaller extent (p < 0.05). L-selectin expression of eosinophils in cocultures was not different from that of eosinophils in conditioned medium. Only anti-granulocyte/macrophage colony-stimulating factor (anti-GM-CSF) reduced the activation of eosinophils in conditioned medium to almost basal levels (p < 0.05). An increase in CD11b expression is mediated by cytokines as well as direct cell contact, whereas a decrease in L-selectin expression is only mediated by cytokines. GM-CSF released by fibroblasts is an important factor in the modulation of both CD11b and L-selectin expression. These results show that lung fibroblasts can activate eosinophils by both adhesive interactions and by soluble factors.

This article has been cited by other articles:

				S. H. P. Oliveira, D. D. Taub, J. Nagel, R. Smith, C. M. Hogaboam, A. Berlin, and N. W. Lukacs Stem cell factor induces eosinophil activation and degranulation: mediator release and gene array analysis Blood, December 15, 2002; 100(13): 4291 - 4297. [Abstract] [Full Text] [PDF]

				F M Spoelstra, D S Postma, H Hovenga, J A Noordhoek, and H F Kauffman Additive anti-inflammatory effect of formoterol and budesonide on human lung fibroblasts Thorax, March 1, 2002; 57(3): 237 - 241. [Abstract] [Full Text] [PDF]

				F. M. SPOELSTRA, H. F. KAUFFMAN, H. HOVENGA, J. A. NOORDHOEK, J. G. R. de MONCHY, and D. S. POSTMA Effects of Budesonide and Formoterol on Eosinophil Activation Induced by Human Lung Fibroblasts Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1229 - 1234. [Abstract] [Full Text] [PDF]

				A. Solomon, R. Shmilowich, D. Shasha, J. Frucht–Pery, J. Pe’er, S. Bonini, and F. Levi–Schaffer Conjunctival Fibroblasts Enhance the Survival and Functional Activity of Peripheral Blood Eosinophils In Vitro Invest. Ophthalmol. Vis. Sci., April 1, 2000; 41(5): 1038 - 1044. [Abstract] [Full Text]