[LTB4-metabolism and histamine liberation by granulocytes in the disease pattern of cystic fibrosis (CF)]

Abstract

We determined the generation and liberation of LTB4 in peripheral granulocytes and the histamine release from basophils in patients suffering from cystic fibrosis (CF, median 17.2 years of age, n = 12). We compared the data with an age matched group of healthy donors (n = 12). All patients suffered from an exacerbation of a chronic pulmonary infection caused by P. aeruginosa. Peripheral granulocytes were stimulated at different days before, during and after antiinfectious treatment with Ca-Ionophore, opsonized zymosan and arachidonic acid. The granulocytes from patients with CF as compared to the control group showed an increased omega-Oxidation of the synthesized LTB4 into 20-COOH- and 20-OH-LTB4 after stimulation with Ca-Ionophore and opsonized zymosan (Ca-Ionophore: ratio of LTB4 versus omega-oxidated products (CF): 0.77 +/- 0.007 mean +/- S.E.M., n = 12, control group: 1.07 +/- 0.1, n = 12, p less than 0.01). Stimulation of the cells with Ca-Ionophore combined with arachidonic acid led to a significantly increased formation of lipoxygenase products in the patient group. No significant differences in the basophil counts were determined between both populations. However, the absolute histamine content per basophil was elevated in the CF group (2.4 +/- 0.3 versus 1.6 +/- 0.2 mean +/- S.E.M., n = 12/12, p less than 0.04). Stimulation of basophils with Ca-Ionophore and anti-IgE leads to a significant higher release of histamine per basophil in CF patients (Ca-Ionophore: 2.6 +/- 0.2 versus 1.3 +/- 0.8 pg/basophil, mean +/- S.E.M., p less than 0.05). These data indicate that basophils in CF may have a greater potential to release mediators. During the antiinfectious treatment a normalization of the altered pattern was observed. Within the CF-groups a strong correlation between the release of LTB4, its metabolites, the histamine release per basophil, the total histamine content and clinical (e.g. pO2 FEV1) and laboratory findings (e.g. IgE and IgG levels, CRP) was established. Our data suggest that the inflammatory process in patients with CF is associated with an alteration of the lipoxygenase pathway and histamine releasability of granulocyte subpopulations which correlates with the clinical signs of inflammation.