Neutrophil peptides, also called defensins, are antimicrobial molecules localized in the azurophil granules of neutrophils. We used a sensitive radioimmunoassay to measure the concentrations of human neutrophil peptides (HNPs) 1-3 in the plasma and blood of 86 healthy volunteers who served as controls and 54 patients with various infections. The respective mean plasma concentrations of HNPs 1-3 in the patients at the onset of bacterial infection, nonbacterial infection, and pulmonary tuberculosis were 4.2, 3.2, and 1.8 times the mean value (+/- SE) for the controls (254.8 +/- 7.1 pg/microL). Plasma concentrations of HNPs 1-3 for the patients were correlated with the peripheral blood neutrophil counts (correlation coefficient = 0.629; P = .0001). The mean concentration (+/- SE) of blood HNPs 1-3 in patients with bacterial infections was higher than the mean value (+/- SE) for controls (10.4 +/- 0.6 ng/microL), whereas the mean concentration (+/- SE) in patients with nonbacterial infections or tuberculosis did not differ from that for controls. Reverse-phase high performance liquid chromatography of plasma samples from patients with bacterial infections showed high concentrations of two precursors of HNPs 1-3, indicating that the biosynthesis of HNPs in neutrophil precursor cells is stimulated in response to infection and/or that the release of pro-HNPs is enhanced. HNPs 1-3 concentrations in the pleural fluid, bronchoalveolar lavage fluid, urine, and cerebrospinal fluid were also elevated in patients with infections. Our results suggest that HNPs have physiological significance in infection and that this family of peptides may be useful in assessing neutrophil function during infection.
Human β-defensin-1 (hBD-1) is a 36-amino-acid antimicrobial peptide that functions in the host innate defense. We developed a highly sensitive radioimmunoassay for hBD-1 and identified several hBD-1 peptides in human kidney, urine, and plasma by amino acid sequencing and mass spectrometry. Large quantities of hBD-1 peptides are produced in the kidney, are released into the tubular lumen as 47-amino-acid pro-hBD1, and then undergo proteolytic processing and generate multiple truncated forms. The respective urine and plasma concentrations of hBD-1 in patients with pyelonephritis are 48.1 ± (SEM) 15.7 pmol/mg creatinine and 2.66 ± 0.41 pmol/ml, 3.1-fold and 1.8-fold those of normal individuals. hBD-1 is thought to contribute to mucosal defense in the urinary tract. Our findings provide a better understanding of the biosynthesis of this peptide and its pathophysiological significance in infectious diseases.
Results-Detectable levels of G-CSF were found in BAL fluid of 83% of patients with IPF while the levels in all healthy volunteers were below the detection limit. In patients with IPF a significant correlation was observed between the BAL fluid neutrophil count and the concentration of G-CSF in the BAL fluid. The neutrophil count also correlated significantly with percentage forced vital capacity. In BAL fluid samples from patients with IPF the mean NCA value was reduced by 35% after neutralisation with an anti-human G-CSF antiserum.Conclusions-G-CSF may be involved in enhancing neutrophil accumulation in the lungs of patients with IPF. (Thorax 1999;54:1015-1020 Keywords: granulocyte-colony stimulating factor; bronchoalveolar lavage fluid; idiopathic pulmonary fibrosis Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is a chronic progressive disorder of the lung parenchyma characterised by both inflammation and fibrosis. 1 Several studies have shown that neutrophils, 2 3 in addition to eosinophils, 4 contribute to the pathogenesis of IPF and increased neutrophil numbers in bronchoalveolar lavage (BAL) fluid are associated with extensive disease. 5 6 However, the mechanisms leading to persistent accumulation of neutrophils in the lung of these patients are not well understood. It is likely that several neutrophil chemotactic factors, such as interleukin (IL)-8, leukotrienes, and granulocyte colony stimulating factor (G-CSF), are released in the lower respiratory tract, attracting neutrophils from the pulmonary capillary blood into the parenchyma. [7][8][9][10] G-CSF, a 20 kD glycoprotein, is known to induce granulopoiesis in vitro and in vivo and to enhance a variety of functions of mature neutrophils. [11][12][13][14][15][16] This cytokine has been shown to be a potent neutrophil chemotactic factor 17 and to enhance the expression of adhesion molecules on neutrophils. 18 These findings suggest that G-CSF may play an important part in the pathogenesis of neutrophil mediated pulmonary disease including IPF. However, to our knowledge, there are no studies that have examined the presence of G-CSF in BAL fluid of patients with neutrophil mediated pulmonary diseases.We therefore measured BAL fluid concentrations of G-CSF in patients with various pulmonary diseases including IPF, and investigated whether G-CSF in the BAL fluid of patients with IPF has neutrophil chemotactic activity. We also investigated the relationship between those concentrations and clinical data in patients with IPF to determine the role of G-CSF in neutrophil accumulation in the lung of these patients. Methods STUDY POPULATIONBAL fluid samples were collected from 16 healthy volunteers (10 men) of median age 28 years (range 19-64), 11 of whom were non-smokers and five were current smokers, and 97 patients with pulmonary diseases (57 men) of median age 58 years (range 22-79), 38 of whom were non-smokers, 43 ex-smokers, and 16 current smokers. These included 24 patients with IPF (12 men) of median age 63 years (ran...
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