Changes in CD11b and L-selectin expression on eosinophils are mediated by human lung fibroblasts in vitro.
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-1beta)-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.
Spoelstra
F M
FM
Departments of Allergology and Pulmonology, University Hospital Groningen, Groningen, The Netherlands.
Hovenga
H
H
Noordhoek
J A
JA
Postma
D S
DS
Kauffman
H F
HF
D000293:Adolescent; D000328:Adult; D000906:Antibodies; D001249:Asthma / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002450:Cell Communication; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004804:Eosinophils / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D019041:L-Selectin / Q000032:analysis* / Q000235:genetics; D008168:Lung / Q000166:cytology*; D016177:Macrophage-1 Antigen / Q000032:analysis* / Q000235:genetics; D010641:Phenotype; D013997:Time Factors
D000906:Antibodies; D017077:Culture Media, Conditioned; D007375:Interleukin-1; D016177:Macrophage-1 Antigen; D019041:L-Selectin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor