Primary role of growth-related oncogene-α and granulocyte chemotactic protein-2 as neutrophil chemoattractants in chronic rhinosinusitis

• Published in: Clinical and experimental allergy 2006-06, Vol.36 (6), p.748-759
• Main Authors: Rudack, C., Sachse, F., Alberty, J.
• Format: Article
• Language: English
• Subjects: Adult; Allergic diseases; Biological and medical sciences; Chemokine CXCL1; Chemokine CXCL5; Chemokine CXCL6; chemokines; Chemokines, CXC - analysis; Chemokines, CXC - immunology; Chemokines, CXC - physiology; Chemotaxis, Leukocyte; Chromatography, High Pressure Liquid - methods; chronic rhinosinusitis; Enzyme-Linked Immunosorbent Assay; epithelium; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glyceraldehyde-3-Phosphate Dehydrogenases - analysis; Glyceraldehyde-3-Phosphate Dehydrogenases - genetics; growth-related oncogene-α (GRO-α); Humans; Immunopathology; Intercellular Signaling Peptides and Proteins - physiology; Interleukin-8 - analysis; Interleukin-8 - genetics; Male; Medical sciences; Nasal Mucosa - immunology; Nasal Mucosa - pathology; Neutrophil Activation; neutrophils; Neutrophils - immunology; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis - immunology; Rhinitis - pathology; Sinusitis - immunology; Sinusitis - pathology
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2006.02501.x

Summary Background The aetiology of chronic rhinosinusitis (CRS) remains unclear. The purpose of this study was to investigate neutrophil‐attracting chemokine patterns in CRS without nasal polyposis. Methods The biological activity of the chemokines was identified using a two‐step high‐performance liquid chromatography (HPLC) technique combined with a bioassay in extracts from 55 CRS patients, and in the turbinate mucosa (TM) of patients (N=51) undergoing septumplasty. The biologic activity of each chemokine was assessed using blocking antibodies to chemokines. Immunolocalization of detected neutrophil chemokines was performed by quantitative evaluation of immunohistochemistry. Besides, PCR analysis was performed to quantify neutrophil chemokine mRNA. Results In CRS, the chemokines primarily detected by two‐step HPLC were growth‐related oncogene‐α (GRO‐α) and the granulocyte chemotactic protein‐2 (GCP‐2). Blocking of GCP‐2 and GRO‐αḋ each resulted in chemotaxis inhibition rates of 43.3% and 35.9%, respectively, whereas anti‐IL‐8 and anti‐ENA‐78 had no effect. Both GCP‐2 and GRO‐αḋ were generally synthesized by the surface epithelium and mucosal glands while GRO‐α in particular was synthesized by endothelial cells, as shown by immunohistochemistry. The concentrations of the chemokines IL‐8 and epithelial cell‐derived neutrophil attractant‐78 (ENA‐78) were low in CRS and TM. Conclusion It appears that both GRO‐α and GCP‐2 contribute to neutrophil chemotaxis in CRS, whereas IL‐8 and ENA‐78 appear to be of secondary importance for the chemotaxis of neutrophils in this condition. The expression of chemokines in mucosal gland cells is the main phenomenon involved in constitutive neutrophil chemotaxis in the TM.