Number Of Pulmonary Macrophages Research Articles

Pulmonary intravascular macrophages regulate the pathogenetic mechanisms of pulmonary lesions during acute courses of classical swine fever.

Classical swine fever (CSF) is a highly contagious and often fatal viral disease of domestic pigs and wild boar. Pulmonary oedema and haemorrhages in lung parenchyma are common lesions in the acute forms of CSF that may compromise pig survival and whose pathogenetic mechanisms remain unclear. The appearance of pulmonary lesions in pigs infected with Alfort/187 strain of classical swine fever virus (CSFV) euthanized between 2 and 17days postinfection (dpi) and the role played by cytokines secreted by different pulmonary macrophage populations in the evolution of lesions was evaluated in this study. Microscopic changes of alveolar septal thickening along with oedema and haemorrhages became more severe at middle-late stages of the experiment. A significant increase in the number of pulmonary macrophages, mainly pulmonary intravascular macrophages (PIMs), was observed coinciding with the onset of alveolar septal thickening from Day 4pi. PIMs were the main target of CSFV from initial stages of infection while the presence of infected pulmonary alveolar macrophages (PAMs) was scarce and late. Initial infection of PIMs induced phagocytic and biosynthetic activation with subsequent release of chemotactic cytokines. TNFα and, to a lesser extent, IL-1α secreted by PIMs were the major cytokines involved, while IL-6 played only a minor role. On the contrary, results suggested only a secondary role of PAMs as source of cytokines. The presence of vascular changes from Day 9pi coincided with the highest levels of infected PIMs and the highest number of pro-inflammatory cytokines secreting PIMs. Activation and phagocytosis of platelets were observed in the lungs of infected pigs from early stages, also coinciding with the expression of cytokines with a proven procoagulant activity. The existence of intravascular coagulation phenomena in lung was ruled out.

Macrophages, Corticosteroids and COPD: What do we know?

The numbers of pulmonary macrophages are increased in COPD. There is evidence that the function of these cells is altered in COPD, and that they contribute to the pathogenesis of the disease. Here we discuss our recently published pooled analysis of five previous macrophage publications. This confirmed that there is no difference in the corticosteroid sensitivity of COPD macrophages compared to controls. We discuss the limitations of corticosteroids for the suppression of macrophage derived CXCL8, which is a neutrophil chemoattractant.  We also discuss recent evidence for myeloid derived cell sub-populations in human lungs, and the relevance to COPD.

The vagus nerve alters the pulmonary dendritic cell response to injury

BackgroundWe have shown previously that vagal nerve stimulation (VNS) protects against burn-induced acute lung injury (ALI). Although the mobilization and activation of immune cells is central to tissue injury caused by the systemic inflammatory response, the specific inflammatory cell populations that are modulated by VNS have yet to be fully defined. The purpose of this study was to assess whether VNS alters inflammatory cell recruitment to the lung after severe burn injury. Materials and methodsMale C57BL/6 mice were subjected to 30% total body surface area steam burn with and without electrical stimulation of the right cervical vagus nerve. The relative levels of pulmonary dendritic cells (DC) and macrophages were compared at 4 h versus 24 h after burn injury. Lung tissue injury was characterized by histology to assess changes in lung architecture, and measure the protein levels of interleukin 6 and transforming growth factor-β1. ResultsSevere burn caused an increase in pulmonary DC recruitment at 4 h after injury that persisted at 24 h after severe burn, whereas there was no change in the number of pulmonary macrophages. In contrast, VNS limited the burn-induced recruitment of pulmonary DC. VNS prevented histologic lung injury and attenuated the release of interleukin 6 and transforming growth factor-β1 in the lung after burn injury. ConclusionsVNS is an effective method to limit pulmonary DC recruitment to the lung and prevent ALI after burn injury. Identifying strategies to limit inflammatory cell recruitment to the lung may have clinical utility in preventing ALI in severely burned patients.

Pulmonary pathology in pediatric cerebral malaria

Respiratory signs are common in African children where malaria is highly endemic, and thus, parsing the role of pulmonary pathology in illness is challenging. We examined the lungs of 100 children from an autopsy series in Blantyre, Malawi, many of whom death was attributed to Plasmodium falciparum malaria. Our aim was to describe the pathologic manifestations of fatal malaria; to understand the role of parasites, pigment, and macrophages; and to catalog comorbidities. From available patients, which included 55 patients with cerebral malaria and 45 controls, we obtained 4 cores of lung tissue for immunohistochemistry and morphological evaluation. We found that, in patients with cerebral malaria, large numbers of malaria parasites were present in pulmonary alveolar capillaries, together with extensive deposits of malaria pigment (hemozoin). The number of pulmonary macrophages in this vascular bed did not differ between patients with cerebral malaria, noncerebral malaria, and nonmalarial diagnoses. Comorbidities found in some cerebral malaria patients included pneumonia, pulmonary edema, hemorrhage, and systemic activation of coagulation. We conclude that the respiratory distress seen in patients with cerebral malaria does not appear to be anatomic in origin but that increasing malaria pigment is strongly associated with cerebral malaria at autopsy.

Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus

SummaryPorcine reproductive and respiratory syndrome (PRRS) is caused by a virus that predominantly replicates in alveolar macrophages. The aim of the present study was to characterize the production of cytokines by subpopulations of pulmonary macrophages in pigs infected by the PRRS virus (PRRSV). Expression of interleukin (IL) 1α, IL-6 and tumour necrosis factor (TNF)-α correlated with the severity of pulmonary pathology and the numbers of pulmonary macrophages. Significant correlations were observed between PRRSV infection and the expression of IL-10, between the expression of IL-12p40 and interferon (IFN)-γ, and between the expression of TNF-α and IFN-γ. These findings suggest that PRRSV modulates the immune response by the up-regulation of IL-10, which may in turn reduce expression of cytokines involved in viral clearance (e.g. IFN-α, IFN-γ, IL-12p40 and TNF-α). The results also suggest that expression of IFN-γ is stimulated by IL-12p40 and TNF-α, but not by IFN-α. All of these cytokines were expressed mainly by septal macrophages with weaker expression by alveolar macrophages, lymphocytes and neutrophils. There appears to be differential activation of septal and alveolar macrophages in PRRSV infection, with septal macrophages being the major source of cytokines.

Increased pathogenesis and inflammation of airways from respiratory syncytial virus infection in T cell deficient nude mice

Respiratory syncytial virus (RSV) infection is ubiquitous and leads to various outcomes between immunocompetent and immunocompromised individuals. This study aimed to compare RSV infection and inflammatory responses between immunocompetent BALB/c mice and immunodeficient nude mice. RSV titers in both infected BALB/c mice and nude mice peaked on the third day post-inoculation, but the nude mice had longer lasting and higher levels of viral replication. RSV infection induced a more severe grade of pulmonary histopathology and larger numbers of leukocytes in airways of nude mice than that of BALB/c mice. RSV infection increased pulmonary macrophages and natural killer (NK) cells in both strains of mice. Furthermore, infected nude mice had larger numbers of pulmonary macrophages and NK cells than infected BALB/c mice. Whereas the RSV infected BALB/c mice secreted more tumor necrosis factor -alpha (TNF-alpha), interleukin-12 (IL-12), interferon-gamma (IFN-gamma) and IL-10 than control BALB/c mice, the infected nude mice had higher levels of TNF-alpha, IL-12 and IL-10 than the infected BALB/c mice. The inflammation induced by RSV infection did not correspond with the immune response of T cells. Macrophages and NK cells were potent immunocytes and inflammatory cells in RSV infection especially when T lymphocytes were deficient. Therefore, nude mice may be a good model for severe and persistent RSV infection in immunocompromised hosts.

INFLAMMATORY RESPONSES AND MUCUS SECRETION IN RATS WITH ACUTE BRONCHIOLITIS INDUCED BY NICKEL CHLORIDE

The effects of inhaled particulate matter in the workplace and outdoor environment on sensitive subpopulations are not sufficiently investigated in human and animal models. Thus, animal models for pulmonary diseases are necessary for appropriate risk assessment of toxic materials. We studied biochemical characteristics of an acute inflammatory process induced by inhalation of nickel chloride aerosols in rats. Acute bronchiolitis was induced by inhalation of nickel chloride aerosols for 5 days in Wistar rats according to the method described by Kyono et al. (1999). Deterioration and recovery from inflammatory responses were evaluated by analyzing markers of inflammation in bronchoalveolar lavage (BAL) fluid. Experimental animals were sacrificed during and after the nickel aerosol exposure period. The number of neutrophils markedly increased to approximately 0.5 × 10 3 cells/µl BAL fluid during nickel aerosol exposure, accompanied by increase of total protein, soluble L-selectin, cytokine-induced neutrophil chemoattractant/growth-regulated gene products (CINC/GRO), elastolytic activity, trypsin inhibitory capacity,β -glucuronidase activity, fucose, and sialic acid in BAL fluid compared with those of the control group. There was correlation between number of leukocytes and soluble L-selectin concentration. The number of pulmonary macrophages in BAL fluid decreased to approximately 15% of those of the control group on the days of nickel aerosol exposure. The level of CINC/GRO recovered to that of the control group on day 3 after cessation of the nickel aerosol exposure. However, other inflammatory markers remained at the elevated levels. Changes in the markers of inflammation during and after the nickel aerosol exposure were consistent with previously reported morphological findings. The results indicated that this animal model is potentially useful as an acute bronchiolitis model.

Contribution of cytokines on the suppression of lung metastasis.

Weekly injection of a protein-bound polysaccharide PSK in mice with Lewis Lung Cancer (LLC) significantly decreased the number of lung metastatic foci concomitant with enhancement of cytostatic activity in the bronchoalveolar lavage (BAL) cells. These effects were more marked when the agent was given intratracheally, inducing a larger number of pulmonary macrophages, lymphocytes and neutrophils concomitant with increases in BAL tumor necrosis factor-alpha (TNF-alpha), mouse inflammatory protein-alpha (MIP-1alpha), mouse inflammatory protein-beta (MIP-1beta), interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6), but not interleukin-2 (IL-2) and interleukin-4 (IL-4). Pre-treatment with anti TNF-alpha antibody reduced these effects. The time course and production of PSK-induced cytokines were similar between the tumor-bearing mice and control mice. BAL neutrophils in mice with LLC showed a tendency toward acceleration of O2- production compared with circulating neutrophils. Pulmonary macrophage phagocytosis was also significantly higher in the LLC mice. These results suggest that enhancement of cytostasis appears to be induced by activation and/or improvement of function in inflammatory and immune cells through cytokines under immunomodulator treatment in lung metastasis, possibly via a TNF-alpha-dependent mechanism.

[A morphological study of pulmonary macrophages in bleomycin-injected murine models].

Pulmonary changes induced in a murine model by intraperitoneal injections of bleomycin were morphologically studied by light and electron microscopy. The number of pulmonary macrophages and the distribution of fibronectin in these cells were evaluated by acid phosphatase and affinity staining using anti-fibronectin horseradish peroxidase conjugates. The onset of acute inflammation occurred 4 days after intraperitoneal injection of bleomycin and reached its peak on the 14th day post-injection. The inflammatory reaction then gradually decreased. Areas of subpleural fibrosis was observed on day 42. On day 14, the ratio of the macrophage in bleomycin-treated mice to that in control mice was 5:1. Many activated and foamy macrophages were observed at that time. These findings indicate that macrophage turnover activity is remarkably increased during the acute inflammatory phase. Fibronectin was detected in the cytoplasm of macrophages on day 14, 21, and 28. It was also detected in both alveolar capillary and epithelial basal lamina as well as in interstitial collagen fibers. On day 42, fibronectin staining was strongly positive in areas of subpleural fibrosis. These results suggest that fibronectin released from pulmonary macrophages plays a role in the process of pulmonary fibrosis.

Effects of 4-ipomeanol on bovine parainfluenza type 3 virus-induced pneumonia in calves.

Previous research has demonstrated that 4-ipomeanol toxicosis can enhance the severity of para-influenza virus-induced pneumonia in mice. The objectives of this study were to determine whether calves are susceptible to 4-ipomeanol-induced enhancement of parainfluenza type 3 viral pneumonia and to determine whether 4-ipomeanol alters pulmonary replication of parainfluenza virus. Male Holstein calves were injected with either 4-ipomeanol (3 mg/kg) or vehicle (polyethylene glycol) 3 days prior to intratracheal inoculation with either parainfluenza virus or sham inoculum of culture medium. Calves in the four treatment groups (ipomeanol-parainfluenza, ipomeanol-medium, vehicle-parainfluenza, and vehicle-medium) were necropsied at 5 days after inoculation with parainfluenza virus or medium. The lungs were studied by correlated methods of light and electron microscopy, digitizing morphometry and pulmonary lavage to quantitate the severity of pneumonia. Pulmonary viral titers were determined, and viral antigen was identified in the lung by immunoperoxidase technique. The calves in the ipomeanol-virus treatment group had over a 9-fold higher (P less than 0.05) volume density of virus-induced interstitial pneumonia than did the calves in the other three treatment groups. This 4-ipomeanol-enhanced viral pneumonia was associated with significantly greater (P less than 0.05) numbers of pulmonary macrophages and neutrophils in the lavage fluid and higher (P less than 0.05) pulmonary titers of pulmonary infectious parainfluenza virus. Four-ipomeanol-enhanced viral pneumonia was characterized in part by extensive hyperplasia of type II alveolar epithelial cells and by dense aggregates of macrophages and neutrophils in alveolar spaces and interalveolar septa. The results indicate that 4-ipomeanol exacerbates interstitial pneumonia in calves induced by bovine parainfluenza type 3 virus.

Increase in the number and the phagocytic function of guinea pig pulmonary and peritoneal macrophages following oral administration of RU 41740, a glycoprotein extract from Klebsiella pneumoniae

RU 41740 (Biostim™) which is a purified glycoprotein extract from Klebsiella pneumoniae, is an orally active non-specific immunostimulant. In guinea pigs, 8 days after a 7 days oral administration of RU 41740 (10 or 100 mg/kg/day), an increase in the cell population of the pulmonary and peritoneal cavities was observed, especially in that of the macrophages. RU 41740 also enhanced the phagocytic activity of both the alveolar and peritoneal macrophages, when their chemotactic activity was not significantly modified. This increase in the number of pulmonary macrophages and the stimulation of their phagocytic function might explain the protective effect afforded by the oral administration of Biostim™ against respiratory infections in patients with chronic bronchitis.

Host defense mechanisms against pneumonia due to Pseudomonas aeruginosa.

Pneumonia due to Pseudomonas aeruginosa is associated with unusually high mortalities. Accordingly, efforts to define better the most important components of lung defenses against this infection are justified as a prelude to defining improved management strategies. In this report, a guinea pig model of experimental aspiration pseudomonas pneumonia was employed for studies of cellular and humoral mechanisms of pulmonary defense. Animals treated with cortisone acetate plus cyclophosphamide experienced decreased survival from pneumonia, and survival rates correlated directly with the degree of myelosuppression. Numbers of pulmonary macrophages and polymorphonuclear neutrophils were reduced in drug-treated animals before impairment of macrophage antibacterial function. Thus, a reduction in numbers of phagocytes alone was sufficient to markedly reduce lung defenses. In additional experiments, normal guinea pigs were vaccinated with a lipopolysaccharide pseudomonas vaccine. Improved survival from pneumonia correlated with high titers of type-specific, heat-stable opsonic antibody. It is concluded that adequate numbers of lung phagocytes, plus type-specific opsonic antibody, represent the ideal status for lung defense against P. aeruginosa infection.

Origin and kinetics of pulmonary macrophages during an inflammatory reaction induced by intra-alveolar administration of aerosolized heat-killed BCG.

This report describes the kinetics of the total population of pulmonary macrophages and their immediate precursors during a slight acute inflammation induced by an aerosol of heat-killed BCG in specific pathogen-free mice. The total number of pulmonary macrophages isolated by lavage and subsequent enzyme digestion of lung tissue rose to 150% of normal in the first 4 h and then diminished gradually, reaching normal levels at 144 h after exposure. The number of monocytes showed a transient rise to 130% of the normal value in the first 24 h after exposure. Analysis of data from 3H-thymidine labeling experiments showed that the increase in pulmonary macrophages was due to the influx of 1.7 × 106 circulating monocytes within 24 h after exposure. In the first 4 h after the aerosol, the monocyte influx rate was 25 times higher than in the normal steady state and then decreased. The frequency of locally dividing pulmonary macrophages, reflected by in vitro labeling, did not differ from that found in animals in th...

Pulmonary inflammatory responses during viral pneumonia and secondary bacterial infection.

Pulmonary bactericidal mechanisms are reduced during viral pneumonia. It has been proposed that secondary bacterial pneumonia occurs because the host's ability to mount an inflammatory response is suppressed. These studies examine the pathobiology of parainfluenza 1 virus and viral-associated staphylococcal pneumonia in a murine model. The sequence of leukocyte and fluid protein changes were studied in the lung and blood. An influx of polymorphonuclear leukocytes into the lungs occurred early in the viral infection, and coincided with lung macrophages aggregation. Maximal increases in pulmonary leukocytes occurred during the period associated with maximum suppression of lung bactericidal mechanisms (days 7-9). During this period, the host was capable of mounting an additional inflammatory response to staphyloccal challenges. Finally, viral pneumonia resulted in a prolonged elevation in the numbers of pulmonary macrophages, lymphocytes, and granulocytes. Thus, changes in lung biology persisted well after resolution of the initiating infections.

Pathologic Sequences from Exposure to Ozone and NO2

Exposure of the lung to ozone and nitrogen dioxide leads to interesting acute and chronic injury. Brief exposure to low levels of these gases results in desquamation of epithelial cells and transitory reduction in the number of pulmonary macrophages. Inflammation of the airway, as evidenced by an influx of polymorphonuclear cells, also occurs at this stage. Very rapid regeneration of epithelial cells occurs, resulting in distinctively altered epithelial pattern, and is fairly complete by 72 hours after exposure. Macrophages also increase in number. If exposure is continued over longer periods of time, chronic changes ensure. These consist of fibrosis of the terminal airway, gross enlargement of the lung, loss of air spaces, and subtle derangement of the connective tissue fibrils. Eventually, the experimentally exposed animals possess an enlarged, inelastic lung occupying a distorted thoracic cage. Other changes will be described from slides.