Characterization of a Novel Chemotactic Factor for Neutrophils in the Bronchial Secretions of Patients with Cystic Fibrosis

Chronic airway inflammation is a hallmark of cystic fibrosis (CF). Biological products with chemotactic activity are essential for neutrophil recruitment to sites of inflammation. The presence of a factor with chemotactic activity higher than that of interleukin (IL)-8 in the bronchial secretions of patients with CF has recently been reported. This article reports that the chemotactic activity of this factor remained unaffected by a variety of physical treatments and could be distinguished from those of IL-8, formylmethionylleucylphenylalanine, leukotreine B4, and platelet-activating factor. The factor induced chemotaxis and chemokinesis locomotion of neutrophils, and its chemotactic activity was sensitive to pertussis toxin and thapsigargin. Semipurified preparation of the chemotactic factor increased transiently intracellular Ca2+ concentration but failed to stimulate the release of neutrophil primary granules and the production of superoxide, suggesting that the semipurified chemotactic factor is a Ca2+-dependent chemoattractant of neutrophils, acting via pertussin toxin-sensitive G protein-coupled surface receptors, that directs neutrophil movement toward the airway epitheliu

Chemotactic Factors in Bronchial Secretions of Cystic Fibrosis Patients

To understand chronic neutrophil attraction into cystic fibrosis airways, both global chemotactic activity and individual chemotactic factors were studied in bronchial secretions. Bronchial secretions of 8 cystic fibrosis patients, collected on the first day of admission for antibiotic treatment, showed a high chemotactic index (19.4 ± 5.7, n = 8). Fractionation by gel filtration of bronchial secretions resulted in three chemotactic fractions. The first factor corresponded to interleukin-8, and the second activated neutrophils via the FMLP receptor. The third factor, which was of lower molecular weight, did not activate FMLP or leukotriene B4 receptors, and its nature is still under investigation. Treating patients with antibiotics reduced global chemotactic activity, mainly by reducing the activity due to stimulation of the FMLP recepto

Neutrophil elastase/alpha1-proteinase inhibitor complex levels decrease in plasma of cystic fibrosis patients during long-term oral beta-carotene supplementation1

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GRO alpha and interleukin-8 in Pneumocystis carinii or bacterial pneumonia and adult respiratory distress syndrome.

Polymorphonuclear leukocytes (PMN) are the predominant inflammatory cells recruited in acute lung injury. This study compares the concentration of interleukin-8 (IL-8) to those of GRO alpha, both of which are CXC chemokines, in bronchoalveolar lavage fluid (BALF) in three acute pathologic states: bacterial pneumonia (BPN); adult respiratory distress syndrome (ARDS); and Pneumocystis carinii pneumonia (PCP). Levels of both IL-8 and GRO alpha were below 5 pg/ml in 16 nonsmoking volunteers who served as controls. Despite more than twice as many neutrophils in the BALF of the BPN group (n = 12) than in the group with ARDS (n = 13), both groups had similar levels of IL-8, of 569 +/- 120 pg/ml and 507 +/- 96 pg/ml, respectively. The GRO alpha concentrations in the BPN and ARDS patients were respectively 3.3 and 3.4 times those of IL-8, reaching 1,870 +/- 314 pg/ml for the BPN and 1,699 +/- 377 for the ARDS patients. In the PCP group (n = 48, 45 human immunodeficiency virus [HIV]-positive, 3 HIV-negative), GRO alpha levels (897 +/- 172 pg/ml) were sevenfold higher than IL-8 levels (123 +/- 40 pg/ml). In all pathologic states there was a good correlation between GRO alpha and IL-8 (r = 0.53, p = 0.0001). GRO alpha or IL-8 both correlate with the absolute neutrophil number/ml when all groups were studied together (r = 0.52, p = 0.0001). Only in the PCP and ARDS groups did IL-8 correlate with the PMN number.(ABSTRACT TRUNCATED AT 250 WORDS