Bronchoalveolar disease in dyskeratosis congenita.

Dyskeratosis congenita (DC) is an unusual familial disorder primarily affecting the skin and its appendages. We report the case of a DC patient with chronic respiratory tract involvement, confirming the features previously reported by a small number of authors: 1) chronic bronchoalveolar involvement is not unusual in this disorder; 2) the main features are early sputum production with subsequent bronchial and alveolar destruction; 3) after onset of dyspnoea the course is rapidly fatal, with progressive respiratory failure. Immune deficiency and repeated bronchoalveolar infections may be involved in the pathogenesis of these manifestations.

Stimulation of arachidonic acid metabolism by adherence of alveolar macrophages to a plastic substrate. Modulation by fetal bovine serum.

In previous studies on arachidonic acid (AA) metabolism by pulmonary macrophages in vitro, we observed that the presence of serum in the culture medium influenced the profile of AA metabolites released. To further characterize this phenomenon, rat alveolar macrophages were placed in plastic tissue culture dishes and allowed to adhere in the presence or absence of 7.5% fetal bovine serum (FBS) for 1 h. Adherent cells were then maintained in medium (equilibration) with or without FBS for 3.5 h before stimulation with the calcium ionophore A23187. The release of thromboxane B2 (TXB2) (the stable metabolite of TXA2) and leukotriene B4 (LTB4) during culture was measured by radioimmunoassay and reverse-phase high pressure liquid chromatography, respectively, at the end of each culture step. Cell adhesion to the plastic substrate in FBS-free medium induced an intense stimulation of AA metabolism, with the release of both TXB2 and LTB4. Adhesion and the accompanying TXB2 release appear to be mediated by trypsin-sensitive components since trypsin-pretreated macrophages showed a dramatic reduction in both adherence and TXB2 synthesis. The presence of FBS during the attachment phase of culture reduced both adhesion and release of TXB2 and LTB4 by more than 50%. On the other hand, addition of FBS to cells that had completed adhesion in serum-free medium stimulated release of both metabolites. When challenged with calcium ionophore after 4.5 h of culture, macrophages that had adhered in FBS-free medium released a much smaller amount of TXB2 than did macrophages that had been cultured in the presence of FBS.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding of iron beads to sialic acid residues on macrophage membranes stimulates arachidonic acid metabolism.

Phagocytosis of carbonyl iron beads by rat alveolar macrophages induces the production of cyclooxygenase and lipoxygenase metabolites of arachidonic acid (AA). To study the relationship between the phagocytic event and AA metabolite production, rat alveolar macrophages were pretreated with cytochalasin D, which suppresses particle internalization, but not binding to the plasma membrane. The cells were then challenged with iron particles. Binding of the particles, without internalization, was a stimulus sufficient to initiate the AA metabolic cascade; this was true for cyclo- as well as for lipoxygenase pathways. To characterize the receptor responsible for iron bead binding to membranes, macrophages were pretreated with the lectin, wheat germ agglutinin. This treatment suppressed iron bead binding, phagocytosis, and the production of AA metabolites. Succinylated wheat germ agglutinin, which binds only to N-acetylglucosamine, prevented none of these events. Wheat germ agglutinin alone had a stimulatory activity on AA metabolism which was biphasic in nature, i.e., production of cyclooxygenase metabolites first and then leukotriene B4 upon rechallenge. Succinylated wheat germ agglutinin was devoid of such an effect on AA metabolism. Thus, AA metabolite production by alveolar macrophages during phagocytosis seems to be stimulated by initial binding of particles to the plasma membrane. Membrane-bound sialic acid residues appear to be instrumental in binding of carbonyl iron beads with consequent initiation of the AA metabolic cascade.

Production of arachidonic acid metabolites by macrophages exposed in vitro to asbestos, carbonyl iron particles, or calcium ionophore.

Consequent to asbestos deposition, alveolar macrophages (AM) accumulate at alveolar duct bifurcations where they phagocytize fibers. Because phagocytosis can stimulate the release of arachidonic acid (AA) metabolites, the possibility that secretion of these powerful mediators of inflammation might be induced by chrysotile asbestos was investigated in vitro. Rat AM were treated in vitro with chrysotile asbestos, and the cyclooxygenase products--prostaglandins, thromboxane B2 (TXB2), 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT)--and lipoxygenase products--leukotrienes (LT), hydroxyeicosatetraenoic acids (HETE)--secreted in the medium were isolated by high-performance liquid chromatography. Composition of the AA metabolites released was compared with that from those stimulated by the calcium ionophore A 23187 (20 microM) and by another particulate phagocytic stimulus, i.e., carbonyl iron beads. Calcium ionophore stimulation induced a marked release of various AA metabolites in the medium from both the cyclooxygenase pathway (HHT, TXB2, and PGE2, in decreasing quantities, respectively) and the lipoxygenase pathway (LTB4, 5-HETE, 12-HETE, and LTC4). The major product was LTB4. Treatment of the macrophages with asbestos fibers induced the release of a similar array of AA metabolites, although there were smaller amounts of LTC4 and 12-HETE, but increased quantities of PGF2 alpha. A time course study showed a steady increase in metabolite production for 1 h, followed by a plateau. In addition, the amount of metabolites released was dependent on asbestos concentrations. Phagocytosis of iron beads induced the secretion of the same metabolites as asbestos stimulation, but in larger quantities, probably reflecting the lack of cytotoxicity of the particle.(ABSTRACT TRUNCATED AT 250 WORDS)

[The prognosis factors of subacute and chronic myelo-monocytic leukemias (author's transl)]. / Les éléments du prognostic des leucémies myélo-monocytaires subaiguës et chroniques.

The myelo-monocytic leukemias (MML) can be of acute, subacute or chronic type, according to the level of bone-marrow blast cells and to the spontaneous course. We have compared the clinical, hematological and biological characters of 11 cases of subacute MML-defined by a survival of less than 12 months - to 20 cases of chronic MML. Anemia, hyperleucocytosis, monocytosis, number of circulating granulocytes and blast cells, level of bone marrow blasts, were superior in acute MML, with significant difference for hemoglobin, circulating and bone-marrow blasts. A high urine lysozyme output, a decrease of granulo-monocytic colonies after bone-marrow culture on semi-solid media were further arguments in favor of the subacute type. This variety, which evolves into acute MML in near 50 p. cent of cases appears consequently as the first step of an acute leukemia, or represents a very close aspect. Chronic MML on the contrary, although with still 30 p. cent blastic transformation, is characterized by a steady course, with a median survival of 3.3 years, and number of untreated patients surviving many years beyond this median time.