Human alveolar macrophages: comparison of phagocytic ability, glucose utilization, and ultrastructure in smokers and nonsmokers.
01 Nov 1970-Journal of Clinical Investigation (American Society for Clinical Investigation)-Vol. 49, Iss: 11, pp 2086-2096
TL;DR: Comparison of the ultrastructural morphology of the alveolar macrophages from each group reveals that the cells from smokers differ from those of nonsmokers in that they are slightly larger, and contain more golgi vesicles, endoplasmic reticulum, and residual bodies.
Abstract: Phagocytic ability, glucose utilization, and ultrastructural morphology were studied in human alveolar macrophages in smokers and nonsmokers. The macrophages were obtained by bronchopulmonary lavage and the studies were carried out in vitro in the absence of smoke. Phagocytic ability was measured as the decrease in the number of viable Staphylococcus albus organisms incubated with the macrophages. Measurements of 14CO2 formation from glucose-U-14C were made in a resting state. 90-95% of the cells obtained by lavage were large mononuclear macrophages of which approximately 90% remained viable at the end of the experiment. Smokers yielded many more macrophages per lavage (mean 46.4 × 106 ±7.4) compared to the nonsmokers (mean 10.2 × 106 ±2.3). The decline in viable organisms was the same in each group, indicating phagocytic competence of alveolar macrophages removed from smokers. However, the mean glucose utilization for the smokers was 4.3 ±0.2 mμmoles/106 cells and 1.4 ±0.7 mμmoles/106 cells for the nonsmokers. This very significant difference (P < 0.0001) suggests that smokers' macrophages have a higher resting energy requirement than those of nonsmokers. Comparison of the ultrastructural morphology of the alveolar macrophages from each group reveals that the cells from smokers differ from those of nonsmokers in that they are slightly larger, and contain more golgi vesicles, endoplasmic reticulum, and residual bodies. The residual bodies in smokers' cells contain distinctive fiber-like inclusions.
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TL;DR: It is postulated that this respiratory bronchiolitis observed in the lungs of young smokers is a precursor of centriacinar emphysema and may be responsible for the subtle functional abnormalities observed in young smokers.
Abstract: The lungs of young smokers and controls of comparable age from a population of sudden non-hospital deaths were systematically studied to determine the relation between cigarette smoking and pathologic changes in peripheral airways. The characteristic lesion observed was a respiratory bronchiolitis associated with clusters of pigmented alveolar macrophages and was present in the lungs of all smokers studied but rarely seen in nonsmokers (p<0.002). The lungs of smokers also showed small but significant increases in mural inflammatory cells and denuded epithelium in the membranous bronchioles as compared to controls (p<0.05). We postulate that this respiratory bronchiolitis is a precursor of centriacinar emphysema and may be responsible for the subtle functional abnormalities observed in young smokers. (N Engl J Med 291: 755–758, 1974)
914 citations
TL;DR: It is suggested that the lung in IPF and CHP may function as a relatively independent immune organ, and that analysis of cells and proteins in broncho-alveolar lavage fluid may be of diagnostic, therapeutic, and investigative value in evaluating patients with fibrotic lung disease.
Abstract: To evaluate cellular and protein components in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP), limited broncho-alveolar lavage was done in 58 patients (19 IPF, 7 CHP, and 32 controls). Analysis of the cells and protein in the lavage fluids from patients with IPF revealed an inflammatory and eosinophilic response and a significant elevation of IgG in the lungs. With corticosteroid therapy, inflammation diminished but eosinophils remained. Lavage fluid from patients with CHP also had eosinophils and elevated levels of IgG. However, in contrast to IPF, lavage fluid from CHP patients contained IgM, fewer inflammatory cells, and a strikingly increased number (38-74%) of lymphocytes. Identification of lavage lymphocytes in CHP showed that T lymphocytes were significantly elevated and B lymphocytes were decreased compared to peripheral blood. These studies suggest nthat the lung in IPF and CHP may function as a relatively independent immune organ, and that analysis of cells and proteins in broncho-alveolar lavage fluid may be of diagnostic, therapeutic, and investigative value in evaluating patients with fibrotic lung disease.
522 citations
TL;DR: Thioglycolate-stimulated mouse peritoneal macrophages secrete a Proteinase which degrades insoluble elastin which exceeds that by primary and established fibroblast cell strains and is likely that elastase secretion by Macrophages plays a major role in the pathogenesis of chronic destructive pulmonary diseases such as emphysema.
Abstract: Thioglycolate-stimulated mouse peritoneal macrophages secrete a Proteinase which degrades insoluble elastin. There is little elastase activity in cell lysates but the bulk of the enzyme accumulates extracellularly during culture in serum-free medium. The secretion of elastase is sustained for over 12 days in culture and continued secretion of elastase requires protein synthesis. Unstimulated macrophages secrete very little elastase activity but can be triggered to secrete higher levels of this enzyme by phagocytosis and intracellular storage of latex particles. The macrophages elastase is a distinctive proteinase differing from the elastases of pancreas and granulocytes and is distinct from the other secreted proteinases of macrophages, namely, collagenase and plasminogen activator. The macrophages elastase is a serine proteinase and is inhibited by di-isopropyl phosphoro-fluoridate, ovoinhibitor, EDTA, dithiothretiol, and serum. Its activity is little affected by soybean trypsin inhibitor, turkey ovomucoid and chloromethyl ketones derived from tosyl lysine, tosyl phenylalanine, and acetyltetra alanine. Hydrolysis by macrophage elastase of chromogenic ester substrates for pancreatic elastase could not be detected. Elastase secretion by stimulated macrophages exceeds that by primary and established fibroblast cell strains. It is likely that elastase secretion by macrophages plays a major role in the pathogenesis of chronic destructive pulmonary diseases such as emphysema.
492 citations
TL;DR: This work defined a discrete pattern of change in animals during the course of tobacco smoke exposure, with the following salient features: systemically, biphasic fluctuations were observed in primary T cell dependent humoral and cellular immune responses, initial enhancement during the first few months of exposure eventually giving way to suppression in chronically exposed animals.
Abstract: Tobacco smoking is associated with increased prevalence of various diseases, both in the respiratory tract and in distal organs. The possibility that tobacco smoke induced changes in immune and inflammatory processes may play a part in the aetiology and pathogenesis of many of these diseases was first recognised in the mid 1960s. The ensuing decade witnessed a steadily increasing research effort centred on toxicological aspects of chronic inhalation of tobacco smoke in relation to immune and inflammatory cell function in experimental animals. This work (reviewed by Holt and Keast') defined a discrete pattern of change in animals during the course of tobacco smoke exposure, with the following salient features: (1) systemically, biphasic fluctuations were observed in primary T cell dependent humoral and cellular immune responses, initial enhancement during the first few months of exposure eventually giving way to suppression in chronically exposed animals; (2) T cell independent immune responses (for example, to bacterial polysaccharide antigens) and secondary immune responses dependent on T memory cells remained normal in these animals; (3) an immediate and profound suppression of T cell function was noted in the respiratory tract, together with (4) the steady development of an expanded and functionally altered population of alveolar macrophages. Recognition of the possibility that similar effects occur in man has provided the impetus for various direct studies on aspects of immune and inflammatory cell functions in human smokers. Furthermore, it has become accepted practice to segregate the smokers within \"control\" populations, particularly in studies using bronchoalveolar lavage. The available data from these human studies are reviewed below in the light of the information available from earlier animal experiments.
375 citations
TL;DR: Observations suggest that the release of interleukin-2 by lung T cells has a central role in increasing the numbers of Lung T cells in active pulmonary sarcoidosis.
Abstract: We investigated the possible role of interleukin-2, a T-cell product that stimulates the clonal increase of responsive T lymphocytes, in the pathogenesis of pulmonary sarcoidosis. We obtained mononuclear effector cells from the lungs of 10 patients with sarcoidosis and high-intensity alveolitis, 17 patients with sarcoidosis and low-intensity alveolitis, 3 patients with idiopathic pulmonary fibrosis, and 10 normal controls. Lung cells from the group with sarcoidosis and low-intensity alveolitis, from the group with idiopathic pulmonary fibrosis, and from the controls produced insignificant amounts of interleukin-2. However, lung cells from 9 of 10 patients with sarcoidosis and high-intensity alveolitis spontaneously released interleukin-2, and in a proportion that correlated with the proportion of T cells in the lung washings (P<0.01). Blood T cells from the same patients did not release interleukin-2. To determine whether release of interleukin-2 by the lung T cells had a biologic effect in vivo,...
344 citations
References
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01 Jan 1964
1,190 citations
TL;DR: This review will limit it self to three aspects of this rapidly enlarging field: (a) Iysosomes in tissue injury and inflammation; (b) IYso somes in immunopathology; and (c) IysoSomes in human disease.
Abstract: Therefore, this review will limit it self to three aspects of this rapidly enlarging field: (a) Iysosomes in tissue injury and inflammation; (b) Iysosomes in immunopathology; and (c) Iyso somes in human disease. Lysosomes comprise a heterogeneous group of cyt oplasmic organelles, the ultrastructural appearance of which in tissues depends upon the history of the particle (5). Lysosomes which have not participated in acts of diges tion arc called "primary lysosomes," the storage-granule form of which is exempli
235 citations
TL;DR: A comparison between polymorphonuclear leucocytes obtained from normal and immune animals revealed no differences in their ability either to ingest or kill coagulase-positive staphylococci.
Abstract: A method has been described for the study in vitro of leucocyte-bacteria interactions which permits the simultaneous evaluation of both phagocytosis and intracellular bacterial inactivation. Employing this technique, the fate and localization of staphylococci in homogeneous suspensions of rabbit polymorphonuclear leucocytes have been studied.
Coagulase-positive strains of S. aureus were not efficiently ingested in the presence of normal rabbit serum. In contrast, coagulase-negative strains of S. albus were rapidly engulfed and inactivated.
Immune sera prepared against a coagulase-positive strain enhanced the the ingestion of the homologous organism as well as of three heterologous strains of S. aureus . Following phagocytosis, prompt intracellular killing of S. aureus occurred. The thermostable opsonins in immune sera reacted only with strains of S. aureus .
A comparison between polymorphonuclear leucocytes obtained from normal and immune animals revealed no differences in their ability either to ingest or kill coagulase-positive staphylococci.
Studies with other bacterial species are presented to illustrate: ( a ) phagocytosis followed by intracellular inactivation; ( b ) phagocytosis followed by intracellular survival; and ( c ) the absence of phagocytosis.
235 citations
TL;DR: CIGARETTE smoking has been recognized as "the most important of the causes of chronic bronchitis" and the pathogenic mechanisms of this relation are incomplete.
Abstract: CIGARETTE smoking has been recognized as "... the most important of the causes of chronic bronchitis. ..."1 Although knowledge of the pathogenic mechanisms of this relation is incomplete it is clear that cigarette smoke produces a variety of morphologic and physiologic changes in the lung. The association of both cigarette smoking and an increased susceptibility to bacterial infection with chronic bronchitis suggests that cigarette smoke directly inhibits antibacterial mechanisms of the bronchopulmonary tree. Defense of the lung against inhaled bacteria is achieved by the mechanism of bacterial clearance.2 A heavy dose of cigarette smoke inhibits bacterial clearance in mice.3 The . . .
181 citations
TL;DR: Serum α1-antitrypsin was shown to inhibit the proteolytic enzymes of human leucocytes, and this finding was interpreted in relation to the association between ai-ant itypsin deficiency and pulmonary emphysema.
Abstract: SummaryProteolytic enzymes from various cellular sources were tested against pro-teinase inhibitors of human serum. Serum α1-antitrypsin was shown to inhibit the proteolytic enzymes of human leucocytes. This finding was interpreted in relation to the association between ai-antitrypsin deficiency and pulmonary emphysema.
130 citations