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Phagocytosis by cells of the pulmonary alveoli. Transformation of crystalline particles.

The progressive transformation of illite crystals in alveolar macrophages has been studied with x-ray microanalysis and electron microdiffraction. Illite particles captured by macrophages undergo a series of progressive modifications which affect their ultrastructure, crystalline state, and chemical composition. Crystalline structure progressively disappears and certain elements are eliminated. At the end of the experiment, which lasted more than 6 months, the initial characteristics of the particles were greatly transformed. The constitutive elements of the illite particles were also found in structures other than macrophages: Type I pneumocytes, interstitium, and blood platelets.

Animals

[Ultrastructural reactivity of the pulmonary alveoli under the influence of the aerosol use of gentamycin and tetracycline].

Studied is the effect of the aerosol application of the gentamycin and tetracycline antibiotics on the ultrastructure of tung alveoli. It is found that these two antibiotics when applied singly and at doses of 0.3024 mg/rat, 1.728 mg/rat and 12.824 mg/rat for the gentamycin and of 1.652 mg/rat and 3.304 mg/rat for the tetracycline may cause catarrhal pneumonia, accompanied by strong fibrinosis of the alveolar septa and of the alveolar basal membrane. The partial or total lysis of nuclear chromation of all alveolar cell nuclei (epithelial, endothelial, septal, and granulated pneomcytes), the nuclei of the blood granulocytes and macrophages included, is established as a specific ultrastructural change.

Aerosols

Pulmonary changes induced by amphophilic drugs.

Administration of amphophilic drugs to experimental animals causes formation of myeloid bodies in many cell types, accumulation of foamy macrophages in pulmonary alveoli, and pulmonary alveolar proteinosis. These changes are the result of an interaction between the drugs and phospholipids which leads to an alteration in physicochemical properties of the phospholipids. Impairment of the digestion of altered pulmonary secretions in phagosomes of macrophages results in accumulation of foam cells in pulmonary alveoli. Impairment of the metabolism of altered phospholipids removed by autophagy induces an accumulation of myeloid bodies. In summary, administration of amphophilic compounds causes a drug-induced lysosomal disease or generalized phospholipidosis.

Animals

[Bronchiolo-alveolar cancer].

The bronchiolo-alveolar adenocarcinoma, less frequent than other types of bronchopulmonary cancers, occurs more frequently during pulmonary fibrosis. Besides a mucous bronchorrhea of little meaning, the clinical manifestations belong to the advanced stages. The X-ray, unreliable and variable, shows a variety of pictures from mono or multinodular ones to pseudopneumonic infiltrates. Usually no information could be derived from bronchoscopy. Positive cytological examination of sputum are unfrequent. Early surgery brings longer remissions than in other types of bronchopulmonary cancer. Diagnosis can only be made from the histology of the exeresis sample. The tumour cells, cuboidal or columnar, are arranged in mono or pluri-stratified layers in the inter-alveolar septa, which progressively become fibrous. This cancer has an original histogenesis: it would originate from the neoplastic metaplasia of type II pneumocytes or of respiratory bronchiole cells, invading the pulmonary alveoli by sliding or by contiguity. Far from the initial foyer, the spreading seems mostly done through airways.

Adenocarcinoma, Bronchiolo-Alveolar

Pulmonary alveolar microlithiasis. A case report with a discussion of differential diagnosis.

The rare disease of pulmonary alveolar microlithiasis is characterized by innumerable microscopic stones, mainly of tribasic calcium phosphate, within the pulmonary alveoli. In a 13-year-old boy an earlier radiological examination showed diffuse lung opacity. The main differential diagnoses taken into consideration were sarcoidosis, idiopathic hemosiderosis, diffuse interstitial fibrosis and alveolar proteinosis. The correct diagnosis was made after a lung biopsy which showed intra-alveolar microliths. The radiological findings are in agreement with the reports in the literature. The specific X-ray features of pulmonary alveolar microlithiasis are calcified opacities, nodules, hilifugal trabeculations and pleural striae. These radiological signs are sufficiently diagnostic to restrict lung biopsy to particularly difficult cases. The disease is resistant to all therapeutic measures.

Adolescent

Pulmonary surface film stability and composition.

Stability of pulmonary alveoli at end expiration requires a very low air-water surface tension (e.g., less than 10 mN.m-1). Another important requirement is that the surface film maintain this low surface tension for a sufficiently long time at fixed lung volume. We measured monolayer collapse rates at 37 degrees C of lung surface-active material (SAM) and certain lipids found in this material and compared them with alveolar monolayer collapse rates calculated from published lung compliance changes. We found collapse rates for purified SAM or a mixture of dipalmitoyl lecithin (DPPC):monoenoic lecithin (PC):cholesterol (CHOL) (3.03:1.65:1 molar ratios) to be much greater than collapse rates of alveolar films estimated from indirect measurements. Monolayers of pure DPPC or DPPC with 10 mol% monoenoic PC and/or CHOL had collapse rates equal to or less than those estimated from lungs. We conclude that the alveolar monolayer is enriched in DPPC to the extent of 90 mol% or greater. Enrichment may exclude more mobile components from the monolayer during expiration when surface tension reaches verry low values.

Animals

[Structure of the interalveolar wall].

The wall, which unites as well as separates two contiguous pulmonary alveoli is composed of: - a conjuntival partition, the veritable skeleton of the wall, which is occupied, to the largest extent, by capillary blood vessels. Between the capillaries, conjunctival cells are dispursed: fibrocytes, fibroblasts and histiocytes, of which some can be mobilised, transformed into macrophages, and penetrate into the alveolar lumen; - modified epithelial cells, whose very thin, vast expansions cover the conjunctival partition; - a liquid film, 0.2 mu in thickness, which separates the epithelial cells, or pneumocytes from the alveolar air. Numerous physiological implications result from this organisation.

Humans

The morphologic changes of the rat type II pneumocytes induced by oxytetracycline.

Ultrastructural changes in pulmonary alveoli of adult Sprague-Dawley rats administered oxytetracycline (1 mg. per ml.) in their drinking water were compared with those of control rats whose drinking water contained no antibiotics. Groups of rats were sacrificed after 4 and 8 weeks of oxytetracycline treatment. Type II pneumocytes of oxytetracycline-treated rats showed an increase in size and number of lamellar bodies, as well as in their cell volume, when compared with controls. Electron microscopic morphometry confirmed these findings; the lamellar inclusion bodies increased 6 and 10 per cent and the cell volume increased 3 and 5 per cent at 4 and 8 weeks, respectively. The type I pneumocyte and alveolar macrophage showed engulfed myelin figures, and the Clara cells appeared quiescent. These findings suggest that the type II pneumocyte hypertrophy can be induced independently from the diffuse alveolar damage. The oxytetracycline treatment may provide a model system in which the pathologic morphology and function of the type II pneumocyte can be studied independently.

Animals

Replenishment of alveolar macrophages in silicosis: implication of recruitment by lipid feed-back.

The deposition of quartz in the pulmonary alveoli creates a major demand for macrophages to replace those destroyed, but local proliferation of monocytes appeared to be minimal and the role of systemic recruitment was therefore explored. Injected silica and lipids stimulated the phagocytic function of the mononuclear phagocytic system (MPS), whilst inhaled silica provoked lipid accumulation in the lung, thus suggesting that lipid might also induce a proliferative response in the marrow. Using marrow cultures, cells of the rat MPS were identified by size and phagocytic capacity for latex microspheres, and then subjected to kinetic analysis in litter-mate pairs by single and double labelling autoradiography, under normal conditions and after administration of lipid extracted from rat lungs consolidated by silica-induced alveolar lipo-proteinosis. Treatment of the results by a new device facilitated distinction of promonocytes from monocytes and thus afforded a more precise means of assessing MPS kinetics. The duration of DNA synthesis and the cell-cycle time of promonocytes were reduced and the rate of entry into DNA synthesis increased as a result of i.v. injection of lung lipid. These findings support the involvement of systemic recruitment of monocytes from the marrow by a positive feed-back mechanism when a powerful irritant persists in the lungs and the results are discussed in the overall context of silicotic fibrogenesis.

Animals

Genes required for Mycobacterium tuberculosis to survive the transition from aerosol to pulmonary alveolar lining fluid and early infection in a model of transmission.

Mycobacterium tuberculosis (Mtb) must withstand physical and chemical stresses during airborne transmission, including during the desiccation of aerosols small enough to reach pulmonary alveoli in a new host. There, Mtb encounters an antimicrobial pulmonary alveolar lining fluid (ALF) before it is engulfed by macrophages. To study the genes involved in Mtb's ability to survive the transition from desiccated droplet to pulmonary alveolus in an in vitro model, we formulated a model alveolar lining fluid (MALF) that mimics the composition of ALF as inferred from human bronchoalveolar lavage fluid (BALF). We compared the transcriptome of log-phase Mtb in MALF to the transcriptome of Mtb in BALF as BALF from the lungs of healthy adults was reconstituted to compensate for the dilution of ALF by lavage (rcBALF). Mtb from log-phase culture in a standard laboratory medium survived quantitatively in MALF and rcBALF for at least 24 hours. In contrast, Mtb that had passed through earlier stages of transmission began to succumb after 3 hours in MALF, past the time when particles have been observed to be phagocytized by alveolar macrophages. Screening of a genome-wide CRISPRi library of Mtb identified 35 genes as uniquely required by Mtb to survive the transition from desiccated microdroplet into rehydration in MALF. Thirty-one of these genes are non-essential under conventional laboratory conditions and seven have unknown functions. Thirteen of the 35 genes were additionally required for Mtb to survive in macrophage-like cells cultured at the air-liquid interface with pulmonary epithelial cells. This study nominates additional members of the transmission survival genome of Mtb, illustrates that different genes may contribute to the survival of Mtb at different stages of transmission, and suggests that modeled transmission can shed light on the functions of Mtb genes whose contributions have been unknown.

Journal Article

Lesions in lambs experimentally infected with bovine respiratory syncytial virus.

Respiratory syncytial virus was inoculated intratracheally into five 1-week-old lambs. Three of the lambs responded clinically with fever, hyperpnea, and listlessness. Pulmonary lesions consisted of multifocal areas of consolidation, with necrosis of individual epithelial cells of the airways and accumulation of necrotic debris, macrophages, and few neutrophils in terminal airways and alveoli. Pulmonary septa in affected areas were infiltrated with numerous macrophages and lymphocytes. Viral particles were seen as buds on epithelial cells and free in bronchioles and alveoli.

Animals