Primary role of growth-related oncogene-alpha and granulocyte chemotactic protein-2 as neutrophil chemoattractants in chronic rhinosinusitis.
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-alpha (GRO-alpha) and the granulocyte chemotactic protein-2 (GCP-2). Blocking of GCP-2 and GRO-alphad 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-alphad were generally synthesized by the surface epithelium and mucosal glands while GRO-alpha 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.


CONCLUSIONS
It appears that both GRO-alpha 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.
Rudack
C
C
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Münster, Münster, Germany. rudack@uni-muenster.de
Sachse
F
F
Alberty
J
J
D000328:Adult; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000032:analysis / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000276:immunology* / Q000473:pathology; D012852:Sinusitis / Q000276:immunology* / Q000473:pathology
C475829:CXCL1 protein, human; C486263:CXCL5 protein, human; C515503:CXCL6 protein, human; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases