Modulatory effects of PKC activity on increased 92-kDa gelatinase secretion by neonatal alveolar macrophages.

We previously demonstrated that alveolar macrophages (AMs) from neonatal rats can secrete more 92-kDa gelatinase than AMs from adult rats. In this study, we investigated the role of the protein kinase C (PKC) pathway in the transductional regulation of 92-kDa gelatinase secretion by rat AMs, and we also evaluated maturational changes in this role with increasing postnatal age. After AM stimulation by phorbol 12-myristate 13-acetate (PMA), we observed a dose-dependent increase in gelatinase secretion that was significantly more marked in AMs from 6-day-old rats than in AMs from adult rats and that was inhibited by the PKC inhibitor calphostin C.

Divergent regulation of 92-kDa gelatinase and TIMP-1 by HBECs in response to IL-1beta and TNF-alpha.

In this study, we addressed the question of whether human bronchial epithelial cells (HBECs) contribute to the regulation of 92-kDa gelatinase activity by secreting tissue inhibitor of metalloproteinase (TIMP)-1. We investigated expression of 92-kDa gelatinase and TIMP-1 in response to lipopolysaccharide (LPS) and to the proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Confluent HBECs from explants were cultured in plastic dishes coated with type I and III collagen.

Alveolar epithelial cells in vitro produce gelatinases and tissue inhibitor of matrix metalloproteinase-2.

Type II pneumocytes are key cells of the alveolar epithelium. They lie on the alveolar basement membrane, which influences their phenotype and functions. We hypothesized that type II pneumocytes degrade basement membrane components by producing gelatinases, members of the matrix metalloproteinase family.

Alveolar neutrophils in endotoxin-induced and bacteria-induced acute lung injury in rats.

Polymorphonuclear neutrophils (PMNs) are thought to play a major role in the pathogenesis of adult respiratory distress syndrome. Because the alveolar epithelium is a decisive factor in alveolo-capillary wall permeability, a toxic effect of emigrated PMNs in alveolar spaces is conceivable. We evaluated alveolar PMN function in two rat models of acute lung injury induced by alveolar instillation of endotoxin [lipopolysaccharide (LPS)] or live Pseudomonas aeruginosa (PYO).

Gelatinases in epithelial lining fluid of patients with adult respiratory distress syndrome.

Gelatinases A and B are matrix metalloproteinases secreted as inactive pro forms and are capable of degrading basement membrane components after activation in the extracellular environment. To determine whether the presence of gelatinases A (noninflammatory cells) and B (inflammatory cells) in epithelial lining fluid (ELF) is associated with the adult respiratory distress syndrome (ARDS), we studied 28 patients divided into four groups based on the presence of ARDS and/or multiple organ failure (MOF). Gelatinase activities were quantified in ELF using zymography.

Nasal cytology in rhinitis children: comparison between brushing and blowing the nose.

Allergic rhinitis is a common disease in childhood, but nasal cytology is rarely used by pediatricians. We compared two techniques of cell sampling, brushing and blowing the nose, among 77 children suffering from chronic rhinitis, of whom 59 were allergic. Staining by the May-Grunwald-Giemsa method enabled the evaluation of the density of cells and especially differential counting of the inflammatory cells.

Oxidant-antioxidant balance in alveolar macrophages from newborn rats.

An oxidant-antioxidant imbalance in neonatal alveolar macrophages (AMs) may contribute to the increased susceptibility to lung injury described in the neonatal period. We therefore evaluated oxygen radical production by rat AMs at various postnatal ages, and measured in parallel cellular antioxidant enzyme activities. AMs were obtained by bronchoalveolar lavage from rats aged < 24 h, 21 days and 5 weeks, and results were compared to those obtained with adult rat AMs.

Efficacy of nebulized budesonide in treatment of severe infantile asthma: a double-blind study.

Background And Objective: Treatments with inhaled corticosteroids yielded conflicting results in infants with severe asthma. The purpose of this study was to assess the efficacy of nebulized budesonide on the control of asthma in this age group.

Methods: In a double-blind, placebo-controlled study, 40 infants with severe asthma received either nebulized budesonide (1 mg) or placebo twice daily for 12 weeks, followed by a follow-up period of up to 12 weeks.

Predominant role of peripheral chemoreceptors in the termination of apnea in maturing newborn lambs.

Apneas are very common and normal in newborns but may become life threatening if they are not terminated appropriately. The aim of this study in newborn lambs was to investigate the influence on apnea termination of postnatal maturation, peripheral chemoreceptor function, and hypoxia. Apneas were induced by passive hyperventilation at varying inspired O2 fraction levels.

Role of gelatinase B and elastase in human polymorphonuclear neutrophil migration across basement membrane.

Polymorphonuclear neutrophil (PMN) migration across basement membrane is thought to be dependent on the degradation of membrane constituents. PMN gelatinase B, a metalloproteinase able to degrade type IV collagen, may be involved in this phenomenon. PMN gelatinase B is released in the extracellular medium as a latent proform and then activated, mainly by PMN elastase.

Unapparent systemic dissemination of Mycobacterium tuberculosis.

A healthy 6-week-old girl exposed to tuberculosis presented a positive DNA amplification for Mycobacterium tuberculosis complex in gastric aspirates and cerebrospinal fluid whereas she had no other clinical or biological symptoms. Cultures were negative. This report underlines the interest of polymerase chain reaction for early diagnosis of tuberculosis and suggests the importance of treating exposed neonates and young infants just as active tuberculosis.

Pulmonary alveolar proteinosis: experience with eight pediatric cases and a review.

We report eight pediatric cases of pulmonary alveolar proteinosis (PAP) that illustrate the polymorphic nature of this disease: two cases with severe neonatal onset, three cases with progressive respiratory distress in patients under 1 year old, and three cases in older children with mild symptoms. Consanguineous parents or affected siblings were identified or suspected in four families. Three patients suffered from associated immune or blood disorders (severe combined immune deficiency, myelodysplasia).

Neutrophil-derived long-lived oxidants in cystic fibrosis sputum.

We evaluated long-lived oxidant potential in the sputum of patients with cystic fibrosis (CF) by quantitating the methionine-inhibitable, long-lived oxidant fraction of sputum, referred to as the chloramines. Taurine, the preferred amino acid substrate for chloramine formation, and myeloperoxidase (MPO), the chlorinated oxidant-generating enzyme, were also quantitated. As compared with the sputum of asthmatic subjects, the sputum of CF patients contained high concentrations of chloramines along with high levels of taurine and active MPO.

Tachykinins induce gelatinase production by guinea pig alveolar macrophages: involvement of NK2 receptors.

To determine whether tachykinins induce gelatinase production by guinea pig alveolar macrophages (AM), and to characterize the mechanism involved, we incubated AM with substance P (SP), neurokinin A (NKA), or the NH2-terminal fragment of SP, SP(1-7). The effects of increasing concentrations of selective NK1 and NK2 agonists on tachykinin-induced gelatinase production were also evaluated, as were the effects of a selective NK2 antagonist. Gelatinase activity in conditioned culture media (CCM) was assessed by zymography and quantified by image analysis.

Imbalance between 95 kDa type IV collagenase and tissue inhibitor of metalloproteinases in sputum of patients with cystic fibrosis.

A growing body of evidence suggests that neutrophil-derived proteinases play a major role in lung tissue damage in cystic fibrosis (CF). Most previous studies have focused on serine proteinases such as neutrophil elastase, providing no information on the extent to which metalloproteinases participate in proteolytic processes in CF. To address this issue, we evaluated the contribution of one of the major neutrophil metalloproteinases, i.

Increased 92 kD gelatinase activity from alveolar macrophages in newborn rats.

The functional immaturity of neonatal alveolar macrophages (AM) may contribute to the increased susceptibility of neonates to lung injury. Because the secretion of proteinases by neonatal AMs may be involved in normal postnatal lung development and in repair after lung injury, we evaluated the capacity of neonatal AMs to secrete 92 kD Type IV collagenase. AMs were obtained by bronchoalveolar lavage from newborn rats at different postnatal ages.

Use of polymerase chain reaction for improved diagnosis of tuberculosis in children.

Objective: To study the value of a rapid diagnostic method based on the amplification by polymerase chain reaction (PCR) of a fragment of the IS6110 insertion element for the detection of Mycobacterium tuberculosis in children.

Design: We tested 199 specimens obtained from 68 children referred for evaluation of suspected tuberculosis.

Results: In 83.

Correlation between activity of beta-lactam agents in vitro and bacteriological outcome in acute pulmonary exacerbations of cystic fibrosis.

A study was conducted to determine whether a direct relationship exists between beta-lactam and/or aminoglycoside activity measured in vitro and bacteriological outcome in acute pulmonary exacerbations of cystic fibrosis. Twenty-seven patients, aged between 6 months and 24 years (mean age 10 1/2 years), were included in the study and received 41 i.v.

Influence of vagal afferents on diphasic ventilatory response to hypoxia in newborn lambs.

The effect of vagal afferents on the ventilatory response to hypoxia was studied in eleven awake newborn lambs. Tests were repeated before and after vagotomy in the same lambs in two conditions: with intact upper airways and after intubation. During hypoxia, a diphasic pattern of ventilatory response was observed in both vagotomized and intact lambs.

Sensitization to inhalant allergens in wheezing infants is predictive of the development of infantile asthma.

Early recognition of infantile asthma in wheezing infants is a major problem for physicians. We investigated whether detection of early sensitization to inhalant allergens would be useful to identify those wheezing infants who are likely to develop asthma. A total of 67 infants (aged 1-25 months) hospitalized for a wheezing episode were initially tested for reactivity to inhalant allergens by both skin prick test and in vitro measurement of specific IgE antibodies (Phadiatop).

Ability of new lung function tests to assess methacholine-induced airway obstruction in infants.

We assessed the ability of innovative lung function tests to detect bronchial obstruction induced by methacholine bronchial challenge. Fifty-five recurrently wheezy infants (mean age 16 +/- 5.2 months) free of respiratory symptoms underwent baseline lung function tests.

Matrix metalloproteinase and elastase activities in LPS-induced acute lung injury in guinea pigs.

Matrix metalloproteinases (MMPs) and elastase are proteolytic enzymes specifically directed against extracellular matrix (ECM) components. They are secreted by inflammatory cells and may consequently contribute to the lesions of the ECM observed during acute pulmonary edema. We therefore evaluated the MMP and elastase activities, which are secreted by cultured alveolar macrophages (AMACs) and polymorphonuclear neutrophils (PMNs) and present in the bronchoalveolar lavage (BAL) fluid in a guinea pig model of acute lung injury induced by intratracheal instillation of lipopolysaccharide (LPS).