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Y Sibille

Publications and source records attributed to Y Sibille.

At least 55 records · Page 3Linked to original sources
PubMed1989

Surface IgA and Fc-alpha receptors on human alveolar macrophages from normal subjects and from patients with sarcoidosis.

Human alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) were found to bear cytophilic IgA and Fc alpha-receptors (Fc alpha R) on their surface. The cytophilic IgA belongs to the IgA1 subclass, but unoccupied receptors can be saturated with either IgA1 or IgA2 molecules. Although both polymeric and monomeric forms could attach, binding was about 5-fold greater for the polymers. Both cytophilic IgA and Fc alpha R are sensitive to trypsin and disappear after 18 h of AM culture. An increase in cytophilic IgA was observed on AM from untreated patients with pulmonary sarcoidosis, but not on AM from steroid-treated patients. A significant correlation was found between IgA levels in BAL and the percentage of AM with cytophilic IgA in normal subjects and in steroid-treated sarcoid patients. However, no such relationship was seen among untreated patients. These data suggest that multiple factors may modulate AM surface receptors for IgA. Inflammatory events occurring in the lungs could alter receptor expression and perhaps be of significance in the immunophysiopathology of certain pulmonary diseases.

Binding, Competitive↗
PubMed1989

Human alveolar macrophages release a factor that inhibits phagocyte function.

Human alveolar macrophages release in vitro a factor that inhibits both random migration and chemotaxis of human polymorphonuclear neutrophils (PMN). This factor is not cytotoxic and is recovered in culture supernatants of alveolar cells from most nonsmoking normal subjects. The inhibitor can be detected 30 min after cell cultures are established and is still produced after 24 h in culture. Its release was inhibited by cycloheximide. When supernatants are separated by molecular sieving (I-60 Waters HPLC column), most of the inhibitory activity is recovered in the low-molecular-weight fractions of the chromatogram (less than 1,000 D). The inhibitor has a broad spectrum of activity against known chemoattractants in that it reduces significantly the chemotaxis of PMN induced by the formyl peptide FMLP, by the complement fragment C5a, and by leukotriene B4; it also decreases the chemotactic activity associated with a monocyte-derived interleukin 1 preparation and the chemotactic activity derived from alveolar macrophage culture supernatants. The inhibitory factor is partially heat labile, is sensitive to aminopeptidase M, and is nonpolar. Both phorbol myristate acetate (PMA) and FMLP-induced superoxide release by PMN are diminished significantly in the presence of this inhibitory factor (p less than 0.01 for PMA and p less than 0.05 for FMLP). The inhibitor also reduces monocyte chemotaxis but has no effect on monocyte random migration. Finally, studies with [3H]FMLP indicate that this inhibitor does not act at the site of receptor binding on PMN. Thus, human alveolar macrophages can release in vitro both neutrophil chemotactic factors and an apparent neutrophil-inhibiting factor that may modulate positively and negatively the movement and the respiratory burst of neutrophils in the alveolar space.

Cell Movement↗
PubMed1989

Relationship between inflammatory processes and gas exchanges in pulmonary sarcoidosis.

In the present study, we investigated whether the analysis of cells and proteins collected by bronchoalveolar lavage (BAL) could accurately reflect the degree of functional impairment in pulmonary sarcoidosis. Eighteen patients with biopsy-proven sarcoidosis were prospectively evaluated. An inverse relationship was demonstrated between BAL coefficient of excretion relative to albumin (RCE) values of IgG and IgA and diffusion for carbon monoxide (Dco). A similar negative correlation existed with PaO2 at the end of a maximal exercise. Steroid therapy in five patients lowered concomitantly BAL RCE of IgA and IgG while Dco values increased. Immunoperoxidase studies in three lung biopsies revealed numerous Ig-containing cells within the lung parenchyma. We suggest that these BAL Ig values reflected the mononuclear cell infiltration of the bronchiolovascular sheaths and lung interstitium. This cellular infiltration likely induces a distortion of the capillary bed and may affect the gas exchanges in a reversible way.

Adult↗
PubMed1989

Clinical and subclinical alveolitis in collagen vascular diseases: contribution of alpha 2-macroglobulin levels in BAL fluid.

The probability that patients with collagen vascular diseases (CVD) will develop fibrosis is unpredictable. Since changes in bronchoalveolar lavage (BAL) cell data can be observed in CVD patients without evidence of lung involvement, we investigated whether the study of soluble components in BAL could help to distinguish CVD patients with lung involvement (n = 15) from those without pulmonary disease (n = 37). Our results demonstrate that the alveolitis observed in patients with overt lung involvement is associated with an increase of BAL alpha 2-macroglobulin (alpha 2-MA). In contrast, the BAL alpha 2-MA levels were found to be normal in CVD patients without evidence of pulmonary disease as well as in CVD patients with overt lung involvement treated with steroids. This was observed even in the presence of high neutrophil or lymphocyte counts in BAL. In conclusion, when neutrophils or lymphocytes accumulate in the lungs of CVD patients without evidence of lung damage, in the majority of patients this cell accumulation is not associated with an increase of BAL soluble components.

Adult↗
PubMed1989

Local increase of antiprotease and neutrophil elastase-alpha 1-proteinase inhibitor complexes in lung cancer.

Tumour progression is dependent on many factors including antiproteases and proteases released by tumour cells or host cells infiltrating the tumour. In the present study, we evaluated the antiprotease content, namely alpha 2-macroglobulin (A2M) and alpha 1-proteinase inhibitor (A1PI) and neutrophil (PMN) elastase complexed with A1PI, in limited and extended lung cancer patients compared to a nonsmoker and smoker control population. Data showed that A2M and A1PI were increased in the involved lung from limited cancer when compared to normals. In extended lung cancer, A2M content was also increased in the uninvolved side. The concentration of PMN elastase-A1PI complex was increased on both sides in lung cancer patients (10.2 ng.ml-1 in the uninvolved side, 8.2 ng.ml-1 in the involved side) when compared to nonsmokers (1.9 ng.ml-1, p less than 0.001) and smokers (3.8 ng.ml-1, p less than 0.005). This increase was not solely due to the smoking habit. We conclude that antiproteases and PMN elastase complexed with antiprotease are increased in lung cancer area. This increase could result in extracellular changes in lung cancer.

Acute-Phase Proteins↗
PubMed1989

[Role of polymorphonuclear neutrophils and deep pulmonary lesions].

The polymorphonuclear neutrophil (PMN) is virtually absent in the alveoli in the healthy subject. On the other hand, in certain infectious and fibrotic pathological states the PMN can invade, sometimes massively, the alveolar and interstitial pulmonary structures. The mechanism of recruitment of the PMN involves both exogenous and endogenous factors including secretory products of the macrophages. PMN is a defensive phagocyte which is often necessary to clear bacteria from the lung. However, through the release of toxic derivatives of oxygen and of proteolytic enzymes the PMN are capable of producing lesions within the pulmonary parenchyma. This double role of defense and aggression makes the PMN an effector cell, which is certainly important but whose activity is not isolated because its function depends mostly on interaction with other cells and mediators.

Humans↗
PubMed1988

Bronchoalveolar cell activation after inhalation of a bronchoconstricting agent.

Airway inflammation is thought to be an important determinant of bronchoconstriction and bronchial hyperreactivity. We have recently demonstrated that bronchoconstriction induced by an aqueous extract of cotton bracts (CBE) is associated with bronchoalveolar complement activation, release of polymorphonuclear neutrophil (PMN) chemoattractants by pulmonary cells, and increased numbers of bronchoalveolar lavage PMN's. In the present study we performed bronchoalveolar lavage (BAL) on subjects after CBE or control (saline) challenge and examined whether BAL cells were activated in vitro to produce other inflammatory agonists. After CBE administration, cultured BAL cells released increased amounts of the reactive O2 species, superoxide (O2-.), and the cyclooxygenase products prostaglandin E2 and thromboxane B2. Although none of these in vitro parameters of BAL cell activation appeared to correlate with the degree of bronchoconstriction induced by CBE, BAL fluid levels of thromboxane B2 were also increased after CBE administration and in vivo amounts of this eicasanoid did correlate with the degree of bronchoconstriction induced by CBE (r = 0.50, P less than 0.04). Finally, although cell culture supernatants were highly chemotactic for PMN's, concentrations of leukotriene B4 were not increased, suggesting other chemotaxins were released by BAL cells in this setting. We conclude that CBE administration activates bronchoalveolar cells to release reactive O2 species and cyclooxygenase products that may be important in the bronchoconstricting response to CBE.

Adult↗
PubMed1988

Antiproteases are increased in bronchoalveolar lavage in interstitial lung disease.

The present study evaluates different cellular and soluble components in the bronchoalveolar lavage (BAL) from patients with interstitial lung disease. We observed an increased T4/T8 lymphocyte ratio in BAL but not in blood from 24 patients with active pulmonary sarcoidosis compared to sixteen normal individuals and to eleven patients with inactive pulmonary sarcoidosis. Seven patients with hypersensitivity pneumonitis had a normal T4/T8 ratio. In the active sarcoidosis and hypersensitivity pneumonitis groups, alpha 1-Protease Inhibitor (alpha 1 PI) in BAL is significantly higher than in the normal group and a significant correlation between the two antiproteases (alpha 2-macroglobulin and alpha 1 PI) is observed. These data demonstrate that antiprotease levels (alpha 1 PI and alpha 2 M) are increased in the lower respiratory tract of patients with interstitial lung disease and that among cellular and soluble components of BAL, alpha 2 M represents a sensitive marker of the alveolitis.

Alveolitis, Extrinsic Allergic↗
PubMed1987

IgA-induced chemokinesis of human polymorphonuclear neutrophils: requirement of their Fc-alpha receptor.

The influence of purified human immunoglobulins on the migration of human neutrophils (PMN) was measured in a 48-well micro chemotaxis chamber, with results expressed as percentages of maximal formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated chemotaxis. Both monomeric and polymeric IgA, of both subclasses, in monoclonal and polyclonal form, as well as secretory IgA and Fc-alpha, but not Fab-alpha fragments, enhanced PMN migration when present either in the lower or in both compartments of the chamber (chemokinesis) at concns as low as 0.1 mg/ml. IgM and IgE had no such effect. In contrast, IgG was chemotactic at low concn (0.1 mg/ml). Both monomeric and polymeric IgA decreased the maximally induced FMLP-chemotaxis, but IgA increased chemotaxis induced by suboptimal levels of FMLP. Binding of 3[H]-FMLP to PMN was not affected. Cytofluorographic analysis revealed that, under the conditions of the assay, IgA did bind to 93% of PMN. Thus, the various forms of IgA have a dual effect on human PMN mobility: (1) increase PMN random migration (chemokinesis); and (2) decrease the maximal FMLP-induced chemotaxis. Our data support the requirement of binding of IgA to the Fc-alpha receptor of PMN for expression of these activities. This effect of IgA on PMN mobility may be relevant in IgA deficiency states.

Antibodies, Monoclonal↗
PubMed1987

Neutrophil chemotactic activity produced by normal and activated human bronchoalveolar lavage cells.

Activated macrophages can secrete a number of mediators that can attract inflammatory cells and enhance secretion of phlogistic substances from these cells. The ultimate effect of activated bronchoalveolar lavage (BAL) cells may be fibrotic lung injury. Inasmuch as pulmonary sarcoidosis is a disease associated with spontaneous activation of macrophages and lymphocytes among BAL cells, cells obtained from patients with sarcoidosis were compared with normal cells. We report that adherent BAL cells in culture from patients with sarcoidosis (n = 21) release during a resting period in vitro more chemotactic activity for neutrophils (PMNs) than do BAL cells from normal individuals (n = 14). After density fractionation of the respiratory cells by albumin gradient, cells from high-density fractions in the group with sarcoidosis secrete more chemotactic activity for neutrophils than cells from less dense fractions. The PMN chemotactic activity spontaneously released in vitro by BAL cells from patients with sarcoidosis correlates with the percentage of PMNs recovered by BAL. Immunochemical bioassay and high-performance liquid chromatographic (HPLC) analysis of BAL cell supernatants revealed a complex pattern of chemotactic factors to be present. Generally, three peaks of chemotactic activity were noted on HPLC 1-60 separations at greater than 20 kd, 8 to 10 kd, and less than 1 kd apparent molecular weights. Significantly, interleukin-1 was present in these supernatants, whereas complement components and leukotriene B4 were absent. Sarcoid BAL cells, principally alveolar macrophages, are activated in vivo as manifested by spontaneous secretion of chemotactic factors for PMNs in vitro. Interleukin-1 and other less well characterized molecules were detected. The presence of PMNs among the lavage cells of some patients with sarcoidosis appears to be an in vivo biologic correlate of this activation. These data provide additional criteria of BAL cell activation in patients with pulmonary sarcoidosis and provide further evidence concerning factors that attract inflammatory cells into the lung.

Bronchoalveolar Lavage Fluid↗
PubMed1986

An in vitro model for polymorphonuclear-leukocyte-induced injury to an extracellular matrix. Relative contribution of oxidants and elastase to fibronectin release from amnionic membranes.

Alteration of the extracellular matrix by inflammatory cells is believed to be important in both lung injury and the subsequent restoration of lung architecture. Here we describe the results of the interaction between an acellular human amnionic membrane model and stimulated human polymorphonuclear neutrophils (PMN) in vitro. Polymorphonuclear neutrophil suspensions were placed on one surface of the amnion, and either the chemotactic peptide FMLP or the cell membrane activator phorbol myristate acetate (PMA) was placed on the opposite side of the amnion. Stroma and basement membrane sides of the amnion were separately exposed to the PMN. The PMN suspension was removed and centrifuged, and the supernatant was assayed for superoxide anion (O2-.) and for elastase activity. Injury to the acellular amnion was evaluated by transmission electron microscopy and by measurement of fibronectin (FN) released from the membrane matrix. Although both stimulants cause a concentration-dependent release of O2-., only PMA stimulated elastase release. These effects were similar when either the stroma or the basement membrane side was exposed to PMN. PMA-stimulated cells and supernatants from PMA-stimulated cells caused solubilization of membrane at different incubation times. Electron microscopy confirmed the disruption of the basement membrane of the amnion by PMA-stimulated PMN. Oxidant scavengers (SOD and catalase) did not prevent matrix degradation, and elastase inhibition by a specific chloromethylketone inhibitor diminished FN release on both sides of the amnion by activated PMN supernatants, but only on the basement membrane side by intact PMN. We conclude that in this model, elastase rather than oxygen radicals solubilizes FN from the matrix.

Amnion↗
PubMed1985

Alpha-2-macroglobulin, monomeric and polymeric immunoglobulin A, and immunoglobulin M in bronchoalveolar lavage.

The concentrations of alpha 2-macroglobulin (alpha 2M), IgM, and the various molecular forms of IgA were measured in unconcentrated bronchoalveolar lavage (BAL) of normal subjects and in that of patients with interstitial lung disease. In BAL of control subjects, as previously observed in other external secretions, orosomucoid-coefficient of excretion relative to albumin (RCE) = 1.1 (albumin RCE = 1)-IgG (RCE = 0.7 in nonsmokers), and alpha 2M (RCE = 0.04) appeared to be secreted mainly by seepage from plasma according to molecular size. The secretion of p-IgA (RCE = 22), IgM (RCE = 0.09), and transferrin (RCE = 1.2) was selective, suggesting either local lung synthesis of these components or their active transepithelial transport. Concentrations of p-IgA, alpha 2M, and IgM in BAL displayed RCE at least 10 times lower than in other external secretions, reflecting the unsignificant local synthesis of these components in alveolar septa. In interstitial lung diseases, including sarcoidosis, hypersensitivity pneumonitis, and other lung fibroses, all protein concentrations in BAL were raised. Increased seepage of plasma proteins across the blood-gas barrier accounted for the elevation of orosomucoid and p-IgA (RCE unchanged). It probably accounted for the appearance in BAL of a characteristic peak of serum type dimeric IgA unbound to secretory component (SC), for the reduced percentage of free SC (5% versus 27% in control subjects), and for part of the increased percentage of m-IgA (52% versus 28% in control subjects). Contribution of local synthesis, presumably by cells infiltrating the alveolar tissue, was indirectly demonstrated for m-IgA and IgG, which were selectively secreted, more than 2-fold greater than albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Effects of a series of chloromethyl ketone protease inhibitors on superoxide release and the glutathione system in human polymorphonuclear leukocytes and alveolar macrophages.

Certain chloromethyl ketone (CH2Cl) protease inhibitors diminish PMA-stimulated (phorbol myristate acetate) superoxide (O-2) release by both human alveolar macrophages (HAM) and polymorphonuclear leukocytes (PMN). Additionally, these compounds diminish glutathione reductase activity (GSSR) and intracellular levels of reduced glutathione (GSH). Inhibitory profiles of these molecules were similar for each of the measured cell products, i.e., TPCK = Z Gly-Leu-Phe-CH2Cl greater than TLCK greater than Meo Succ-(Ala)2-Pro-Val-CH2Cl. Because Meo Succ-(Ala)2-Pro-Val inhibited GSSR in cell sonicates but not in intact cells, it appears that all these effects are closely related to the cell penetration by these CH2Cl compounds. We conclude that (1) inhibition of O-2 release in PMN and HAM by CH2Cl does not necessarily implicate a surface protease in O-2 production, (2) some of these compounds certainly impair the intracellular glutathione redox system necessary for the respiratory burst, and (3) only the nonpenetrating inhibitor Meo Succ-(Ala)2-Pro-Val-CH2Cl can be used to distinguish injury caused by extracellular protease (elastase) from that caused by superoxide anion.

Amino Acid Chloromethyl Ketones↗
PubMed1983

Three-drug chemotherapy combined with radiation therapy in small cell carcinoma of the lung.

In 43 cases of small cell carcinoma of the lung, a combined treatment has been initiated with three drugs (cyclophosphamide 750 mg/m2, adriamycin 50 mg/m2 and vincristine sulphate 1 or 2 mg total dosage), split-course-radiation therapy on the primary tumour (3500 rads) and prophylactic irradiation of the brain (2000 rads). The median survival of the 34 cases evaluable at day 50 attains 253 days. A more favourable evolution is observed for patients with a good response after therapy (median survival: 315 days) and for cases with limited disease (321 days) than for non-responders (median survival: 157 days) and for cases with extensive disease (median survival: 214 days). In spite of tumour site irradiation, prophylactic irradiation of CNS and chemotherapy, there were six local relapses, two CNS extensions and six metastatic relapses and only two autopsied cases without macroscopic evidence of relapse.

Adult↗