Polymorphism of the eosinophil cationic protein-gene is related to the expression of allergic symptoms.

BACKGROUND: We have found a polymorphism in the ECP (eosinophil cationic protein)-gene at position 434 according to GenBank accession number NM 002935. This polymorphism would cause the change of the amino acid arginine (base at position 434 is G) at position 97 to threonine (base at position 434 is C). OBJECTIVE: To investigate the prevalence of the ECP-polymorphism and to screen for disease associations. METHODS: DNA of 209 medical students and 76 asthmatic subjects was analysed. The 434 genotype in the ECP-gene was detected by cleavage of the amplified DNA sequence with the restriction enzyme PstI and analysis of the cleaved product by agarose gel electrophoresis. RESULTS: The prevalences of the polymorphism in the student population were 53%, 39% and 8% for the 434GG, the 434GC and the 434CC genotype, respectively, with allele frequencies of 72% (434G) and 28% (434C). Subjects reporting allergy had a higher prevalence of the 434G allele than non-allergic subjects (P = 0.0056). Of the students who were Phadiatop-positive and had allergic symptoms, 79% had the 434GG genotype, whereas the 434GC and 434CC genotypes were present in 82% of those who did not express allergic symptoms (P < 0.001). Among the 76 patients with asthma, patients with allergic asthma had a significantly higher proportion of 434GG compared with patients with non-allergic asthma (P = 0.04). None of the 18 subjects of the two groups with the 434CC genotype had allergy. CONCLUSION: The 434(G > C) polymorphism in the ECP-gene is related to the development of allergic symptoms, suggesting a central role for the ECP molecule in the process.

Effects of in vivo administration of G-CSF on neutrophil and eosinophil adhesion.

The effect in vivo of G-CSF on neutrophil and eosinophil adhesion was studied after subcutaneous administration to six healthy individuals of human recombinant glycosylated G-CSF (lenograstim) (3 micrograms/kg) for 6 consecutive days. Basal adhesion and adhesion to E-selectin. VCAM-1 and ICAM-1 of neutrophil and eosinophil granulocytes were measured selectively. During G-CSF administration neutrophil basal adhesion increased from 7.4 +/- 3.9% (mean +/- SD) to 55.8 +/- 12.9% and 23.2 +/- 4.4%, 4 and 7 d, respectively, after start of the administration. At the same time points eosinophil basal adhesion increased from 7.1 +/- 2.4% to 37.7 +/- 6.1% and 13.1 +/- 5.3%, respectively. When adhesion was measured in the presence of Mn2+, which increases the functional activity of integrins, an even higher increase of neutrophil and eosinophil basal adhesion was noted 4 and 7 d, respectively, after start of G-CSF administration. In parallel with the enhanced basal adhesion neutrophil adhesion to E-selectin and ICAM-1 and eosinophil adhesion to E-selectin. VCAM-1 and ICAM-1 were significantly (P < 0.05) increased after 4 d of G-CSF administration as was neutrophil cell surface expression of CD11b and CD18. In vitro G-CSF induced minimal changes of granulocyte basal adhesion and inhibition of the adhesion to E-selectin. 10 ng/ml TNF alpha significantly increased neutrophil and eosinophil basal adhesion and adhesion to VCAM-1 and ICAM-1. In summary, administration of G-CSF to healthy subjects induced enhanced adhesion of neutrophil and eosinophil granulocytes, probably mediated by an increase of the functional capacity of beta 1- and beta 2-integrins. The induction of increased levels of TNF alpha might be one mechanism behind the in vivo effect of G-CSF administration.