Glucose Stimulates Phagocytosis of Unopsonized Pseudomonas aeruginosa by Cultivated Human Alveolar Macrophages

Glucose has previously been shown to increase the in vitro phagocytosis of unopsonized Pseudomonas aeruginosa by freshly explanted murine peritoneal macrophages (PM) and cultivated alveolar macrophages (AM). This study examined the effect of glucose on the same phagocytosis process in human AM in order to determine whether this phenomenon is conserved among species. Freshly explanted human AM phagocytosed unopsonized P. aeruginosa at a low level (2 bacteria/macrophage/30 min), whereas mouse AM ingested a negligible number of P. aeruginosa (0.01 bacterium/macrophage/30 min). Glucose had no effect on this or other phagocytic processes in freshly explanted mouse or human AM. However, following in vitro cultivation for 72 h, human AM phagocytosed three to four times more unopsonized P. aeruginosa than did freshly explanted cells, but only in the presence of glucose. This glucose-inducible phagocytic response had also been observed in cultivated murine AM. Although similar increases were also detected for the phagocytosis of latex particles and complement-coated sheep erythrocytes by cultivated human AM, these processes were not glucose dependent. The lack of response to glucose in freshly explanted mouse AM was attributed to insufficient glucose transport; however, freshly explanted human AM exhibited significant facilitative glucose transport activity that was inhibitable by cytochalasin B and phloretin. Taken together, these results suggest that the process of glucose-inducible phagocytosis of unopsonized P. aeruginosa is conserved among macrophages from different species, including humans, and that AM, but not PM, required cultivation for this glucose effect to occur. Glucose transport by AM appears to be necessary but not sufficient for phagocytosis of unopsonized P. aeruginosa.     

Effect of Trace Metals on Phagocytosis by Alveolar Macrophages

Experiments were performed to measure the effect of trace metals on a vital function of the alveolar macrophage (AM), phagocytosis. Since certain trace metals were found to reduce the viability of AMs, a technique was developed to permit examination of live cells only for phagocytosis. Evidence is presented that Ni(2+) selectively altered the phagocytic activity of AMs at concentrations lower than those which caused cell death. It is further shown that a level of VO(3) (-) that caused extensive lysis and death did not reduce phagocytosis in surviving cells. The effects of Cd(2+), Cr(3+), and Mn(2+) on AMs were also examined.     

Phagocytosis and Killing of Francisella tularensis by Human Polymorphonuclear Leukocytes

Bacteria of a wild strain of Francisella tularensis were less efficiently killed by human polymorphonuclear leukocytes than were bacteria of an attenuated strain. This finding was explained to some extent by a less efficient phagocytosis, but bacteria of the wild strain also seemed to be more resistant to killing after ingestion.     

In Vitro Sperm Phagocytosis by Human Peritoneal Macrophages in Endometriosis-Associated Infertility

PROBLEM: The mechanism of infertility in women with endometriosis remains obscure. In this context the role of peritoneal macrophage's sperm phagocytic ability in infertile women with and without endometriosis was investigated. METHOD: Analysis of peritoneal macrophage concentration and in vitro sperm phagocytosis in 10 infertile women with endometriosis and 10 infertile women without endometriosis was carried out. RESULTS: It was observed that infertile women with endometriosis are associated with higher concentration and higher sperm phagocytic activity of peritoneal macrophages than those without endometriosis. CONCLUSION: Despite the small number of women in this study, it may be concluded that the increased number of peritoneal macrophages coupled with enhanced in vitro sperm phagocytosis may disturb fertilization and thereby cause infertility.     

Kinetics of Phagocytosis and Intracellular Killing of Candida albicans by Human Granulocytes and Monocytes

The study of the phagocytosis and intracellular killing of Candida albicans by granulocytes and monocytes has been hampered by the budding and pseudomycelium formation of this yeast during a relatively short incubation period at 37 degrees C and by the similar density of candida cells and phagocytes, which makes differential centrifugation impossible. In the present study, C. albicans was used after 5 days of preculture at 30 degrees C, after which the number of candida cells remained constant during incubation at 37 degrees C for 90 min. On this basis, phagocytosis and intracellular killing were limited to a period of 60 min. Phagocytosis of C. albicans by granulocytes and monocytes was measured with a hemocytometer, the number of extracellular candida being a measure of the ingestion of these microorganisms. After 60 min, 96% of the candida cells were ingested by normal human granulocytes and monocytes. This process was dependent on the opsonin concentration and temperature and was inhibited by mono-iodoacetic acid. Heat-inactivated serum was less active than fresh serum, reflecting the role of complement factors with respect to opsonization. Intracellular killing was measured by a microbiological assay. After 60 min of incubation of phagocytes together with C. albicans and serum, human granulocytes and monocytes killed 58 and 50% of the ingested candida, respectively. This process was inhibited by phenylbutazone. Phagocytes from patients with chronic granulomatous disease showed impaired intracellular killing.     

Toll-Like Receptor Stimulation Enhances Phagocytosis and Intracellular Killing of Nonencapsulated and Encapsulated Streptococcus pneumoniae by Murine Microglia

Toll-like receptors (TLRs) are crucial pattern recognition receptors in innate immunity that are expressed in microglia, the resident macrophages of the brain. TLR2, -4, and -9 are important in the responses against Streptococcus pneumoniae, the most common agent causing bacterial meningitis beyond the neonatal period. Murine microglial cultures were stimulated with agonists for TLR1/2 (Pam₃CSK₄), TLR4 (lipopolysaccharide), and TLR9 (CpG oligodeoxynucleotide) for 24 h and then exposed to either the encapsulated D39 (serotype 2) or the nonencapsulated R6 strain of S. pneumoniae. After stimulation, the levels of interleukin-6 and CCL5 (RANTES [regulated upon activation normal T-cell expressed and secreted]) were increased, confirming microglial activation. The TLR1/2, -4, and -9 agonist-stimulated microglia ingested significantly more bacteria than unstimulated cells (P < 0.05). The presence of cytochalasin D, an inhibitor of actin polymerizaton, blocked >90% of phagocytosis. Along with an increased phagocytic activity, the intracellular bacterial killing was also increased in TLR-stimulated cells compared to unstimulated cells. Together, our data suggest that microglial stimulation by these TLRs may increase the resistance of the brain against pneumococcal infections.Immunocompromised patients have a higher risk of developing bacterial infections in the central nervous system (CNS) (34, 37, 42). The list of the pathogens includes many organisms with low pathogenicity in the immunocompetent host (34, 37). Moreover, the distribution of the pathogens also differs from the immunocompetent host and depends on the nature of the immune defect. Patients with a decrease in B-lymphocyte function or with a loss of splenic function have an increased risk of meningitis caused by encapsulated bacteria, while patients with an impaired T-lymphocyte-macrophage system are more susceptible to CNS infections caused by intracellular pathogens (7, 42). One additional cause of this increased susceptibility to CNS infections probably is a decreased local immune defense (33).CNS infections not only are more frequent but also are associated with higher mortality rates and more severe long-term sequelae in immunocompromised than in immunocompetent individuals (9, 17, 34, 44). Polymicrobial infections, multiple organ system presentation, and the absence of typical clinical manifestations subsequent to the host''s diminished inflammatory response are challenging aspects in the management of these infections (34, 37, 42).The brain tissue shows a well-organized innate immune reaction in response to bacteria in the cerebrospinal fluid (CSF) (3, 21). Microglial cells, the resident phagocytes of the CNS, express Toll-like receptors (TLRs) that identify pathogen-associated molecular patterns (PAMPs) (41). The receptor-ligand interactions activate microglia to undergo morphological transformation as well as functional changes, such as the production of proinflammatory cytokines, chemokines, and reactive oxygen species, enhanced phagocytic activity, and antigen presentation (15, 39). This immune reaction cannot eliminate high amounts of pneumococci from the CSF but does prevent or minimize the invasion of these pathogens into the brain tissue, thereby limiting tissue destruction and neuronal injury.TLR2, -4, and -9 contribute to the recognition and response to Streptococcus pneumoniae in the CNS (31). A deficiency of TLR2, -4, or -9 or of the coreceptor CD14, which is necessary for TLR4 signaling increases the susceptibility of mice to S. pneumoniae (1, 11, 12, 40).Here, we hypothesized that activation of the innate immune response in microglia could increase the resistance of the brain tissue against CNS pneumococcal infections (14). This may be of particular interest in immunocompromised patients, whose outcome after S. pneumoniae meningitis is worse than that of immunocompetent individuals (9, 44). The aim of the present study was to investigate whether the stimulation of microglia by respective PAMPs can increase their ability to phagocytose and kill intracellular nonencapsulated and encapsulated S. pneumoniae strains, thereby protecting the brain during meningitis. Moreover, by using an encapsulated and a nonencapsulated pneumococcal strain, we assessed the protective effect of the capsule against phagocytosis by microglial cells.     

Kinetics of Phagocytosis and Intracellular Killing of Staphytococcus aureus and Escherichia coli by Human Monocytes

Tie kinetic patterns of the phagocytosis and intracellular killing of Staphytococcus and Echerichia coli by monocytes were investigated separately to acquire more insight into the total process, i.e. from the ingestion to the death of the micro-organisms. Phagocytosis proved to be dependent on: (1) both the bacteria-to-monocyte ratio and the monocyte concentration; a concentration of at least 5 × 10⁵ monocytes/ml proved necessary for the measurement of ingestion, whereas the rate of ingestion was found to be proportional to the number of extracellular bacteria until a maximum rate is reached, (2) the serum concentration in the incubation medium, which influenced both the rate of phagocytosis and the maximum number of bacteria taken up by one monocyte, and (3) the temperature, the highest rate of phagocytosis being reached at 37–41°C The intracellular killing proved to be dependent on: (1) the number of bacteria ingested; the rate of killing was proportional to the number of ingested bacteria until a maximum rate was reached; (2) the temperature, since a maximum rate of killing is only reached at 37–41°C: at tower and higher temperatures the rate of killing is lower, in the latter case due to inactivation of extracellular stimuli. These separate data on the ingestion and killing processes made it possible to compute the theoretical numbers of extracellular, viable intracellular, and total intracellular bacteria for a model system consisting of 5×10⁶ monocytes, 5×10⁶ bacteria, and 10% serum. These calculated values are in agreement with the experimental data.     

Streptococcus pyogenes Triggers Activation of the Human Contact System by Streptokinase

Severe invasive infectious diseases remain a major and life-threatening health problem. In serious cases, a systemic activation of the coagulation cascade is a critical complication that is associated with high mortality rates. We report here that streptokinase, a group A streptococcal plasminogen activator, triggers the activation of the human contact system. Activation of contact system factors at the surface of the Streptococcus pyogenes serotype M49 is dependent on streptokinase and plasminogen. Our results also show that secreted streptokinase is an efficient contact system activator, independent from a contact surface. This results in the processing of high-molecular-weight kininogen and the release of bradykinin, a potent vascular mediator. We further investigated whether the ability of 50 different clinical S. pyogenes isolates to activate the contact system is associated with an invasive phenotype. The data reveal that isolates from invasive infections trigger an activation of the contact system more potently than strains isolated from noninvasive infections. The present study gives new insights into the mechanisms by which S. pyogenes triggers the human contact system and stresses the function of soluble and surface located plasmin exploited as a group A streptococcal virulence factor through the action of streptokinase.     

Subpopulations of Human Lung Alveolar Macrophages: Ultrastructural Features

Lung alveolar macrophages (LAM), obtained by bronchoalveolar lavage of healthy donors, were separated into four subfractions on discontinuous gradients of Percoll and subjected to light micro-scopic, transmission (TEM) and scanning electron microscopic (SEM) studies. Alveolar macrophage morphometric analysis was performed on cytocen-trifuged preparations. TEM of subpopulations revealed considerable morphologic heterogeneity. By SEM, cells of the most dense (D) subtraction were small, round, and, typically, the surface was highly ruffled with small membrane pseudopods. Cells of the least dense subtraction (A) showed a low degree of membrane folding or filopodia and were often totally disorganized.

In smokers, macrophages of fraction A had a greater area and perimeter compared with non-smokers, whereas the inverse relationship was observed for C and D cells. Also, the number of electron-dense inclusions and the level of acid phosphatase were higher in smokers than in non-smokers. Coupled with functional heterogeneity the morphologic differences described in this paper suggest that density-separated subpopulations of LAM may represent different stages of differentiation or maturation.     

Invasive infections by Streptococcus pyogenes

Invasive infections by Streptococcus pyogenes continually increase both in France and in others industrialized countries. Because of the seriousness, the rapidity of the evolution and the epidemic potentialities, guidelines for managing these infections are requested by the Superior Council of Public Hygiene of France. The authors report herein a case of an adult stricken down by a violent evolution due to Streptococcus pyogenes. They point up how diagnosis, treatment and prophylaxis for family circle are difficult.     

Modulation of Mitogen-Induced Proliferation of Autologous Peripheral Blood Lymphocytes by Human Alveolar Macrophages

Experiments were carried out to determine the effect of cocultivation of T-cell-enriched human peripheral blood lymphocytes with autologous alveolar macrophages on mitogen-induced proliferation as determined by [³H]thymidine uptake. Cells obtained by fiberoptic bronchoscopy and saline bronchial lavage from 14 normal volunteers were enriched for macrophages by adherence in plastic dishes for 1 h in RPMI 1640 medium supplemented with 10% fetal calf serum. Nonadherent mononuclear cells were prepared from heparinized venous blood after Ficoll-Hypaque sedimentation by passage over nylon wool columns. T-cell-enriched populations were incubated with and without alveolar macrophages, either in the presence or absence of phytohemagglutinin. In these experiments, the number of lymphocytes was held constant (10⁵ per well), while the number of alveolar macrophages was varied (0.1 × 10⁵ to 4.0 × 10⁵ per well). Alveolar macrophages generally tended to stimulate phytohemagglutinin-induced lymphoproliferation at lymphocyte/macrophage ratios of 10:1 but consistently and significantly suppressed proliferation at ratios which approach those usually observed in recovered human bronchial lavage fluid, namely, 1:4. The suppressive effect of alveolar macrophages was observed as early as 48 h after culture initiation, while the magnitude of suppression increased with time. Suppression did not appear to be due to alteration in lymphocyte viability, nor was it sensitive to indomethacin. These results indicate that human alveolar macrophages can modulate the in vitro proliferative response of autologous peripheral blood lymphocytes. This observation may have relevance to interactions between alveolar macrophages and bronchial lymphocytes in the human lung in vivo.     

Cigarette Smoke Exposure Impairs Pulmonary Bacterial Clearance and Alveolar Macrophage Complement-Mediated Phagocytosis of Streptococcus pneumoniae

Cigarette smoke exposure increases the risk of pulmonary and invasive infections caused by Streptococcus pneumoniae, the most commonly isolated organism from patients with community-acquired pneumonia. Despite this association, the mechanisms by which cigarette smoke exposure diminishes host defense against S. pneumoniae infections are poorly understood. In this study, we compared the responses of BALB/c mice following an intratracheal challenge with S. pneumoniae after 5 weeks of exposure to room air or cigarette smoke in a whole-body exposure chamber in vivo and the effects of cigarette smoke on alveolar macrophage phagocytosis of S. pneumoniae in vitro. Bacterial burdens in cigarette smoke-exposed mice were increased at 24 and 48 h postinfection, and this was accompanied by a more pronounced clinical appearance of illness, hypothermia, and increased lung homogenate cytokines interleukin-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor alpha (TNF-α). We also found greater numbers of neutrophils in bronchoalveolar lavage fluid recovered from cigarette smoke-exposed mice following a challenge with heat-killed S. pneumoniae. Interestingly, overnight culture of alveolar macrophages with 1% cigarette smoke extract, a level that did not affect alveolar macrophage viability, reduced complement-mediated phagocytosis of S. pneumoniae, while the ingestion of unopsonized bacteria or IgG-coated microspheres was not affected. This murine model provides robust additional support to the hypothesis that cigarette smoke exposure increases the risk of pneumococcal pneumonia and defines a novel cellular mechanism to help explain this immunosuppressive effect.Pneumococcal pneumonia, caused by the Gram-positive pathogen Streptococcus pneumoniae, is the most common form of community-acquired pneumonia in the United States and worldwide (24, 26). This organism can disseminate from the respiratory tract and is the leading cause of death from invasive bacterial infections, with antibiotic-resistant strains becoming increasingly more common (18, 26). Cigarette smoke (CS) exposure increases the risk of serious pneumococcal infections in humans (2, 29), although the mechanisms underlying this effect are not known. Consistent with increased risks of many infectious diseases among smokers (3), animal models have been used to demonstrate impairments in host defense against viral (13, 33), fungal (8), and bacterial (11) infections in smoke-exposed animals. To our knowledge, no reports exist which demonstrate the effects of CS exposure on host defense in a murine model of pneumococcal pneumonia, despite the clinical significance of this pathogen.The alveolar macrophage (AM) is a specifically differentiated resident phagocyte in the pulmonary alveoli that acts to maintain an environment free of pathogens and debris (27). Under normal conditions, AMs constitute the majority of immune cells within the alveolar space and act as a first line of innate host defense in the lung, using an array of receptors to recognize pathogen-associated molecular patterns (PAMPs) and to facilitate phagocytic uptake (36). Normally, AM function is tightly regulated to prevent inappropriate inflammation that could result in lung damage (1), but under conditions which overwhelm their clearance capacity, AMs play additional roles in the generation and subsequent resolution of inflammation and leukocyte recruitment (28, 37). Murine models of pulmonary pneumococcal infection have shown increased mortality (22) and bacterial burden (10) following AM depletion, indicating their importance in the innate host defense against such infections. Phagocytosis of S. pneumoniae is enhanced following opsonization with complement fragments C3b and C3bi, which adhere to the surfaces of bacteria. The critical importance of C3 in this context was recently demonstrated by studies reporting defects in host defense against pneumococcal pneumonia (19, 34).The increased susceptibility of smokers to pneumococcal pneumonia is incompletely understood, and no reports to date have assessed the effects of CS exposure on AM phagocytosis of pneumococcus, although many studies have demonstrated impairments in phagocytosis of other targets (15, 16, 21, 30, 31). Therefore, we determined the effects of CS exposure on pulmonary host defense against pneumococcal pneumonia in a murine model and assessed the effects of CS on AM phagocytosis of S. pneumoniae in vitro.     

Synthesis of Soluble C3 and C9 Neoepitopes by Human Alveolar Macrophages in Vitro

The aim of this study was to examine whether soluble neoepitopes of activated C3 (C3b, iC3b, C3c) and C9 are produced by human alveolar macrophages cultured in serum-free medium. There was a significant and inhibitable production of C3 and C9 neoepitopes and C9 by the macrophages from all donors, as detected by enzyme-linked immunosorbent assays based on monoclonal (bH6, aE11) and polyclonal (anti-C9) antibodies. A strong donor-dependent variation in the levels of the C3 neoepitope and C9 (five- to sevenfold) and the C9 neoepitope (twofold) was found. After 1 day (24 h) of incubation, the complement levels were largely unaltered. The presence of an exogenous alternative pathway activator (agarose beads) reduced the amount of soluble complement because of binding to the agarose. However, the relative fraction of C9 neoepitope versus C9 increased (two- to threefold), due to agarose-mediated activation of C9. The results demonstrate activation of the complement system in serum-free alveolar macrophage cultures, irrespective of the presence of a known complement activator.     

Chemotactic Responsiveness of Human Alveolar Macrophages: Effects of Cigarette Smoking

Pulmonary alveolar macrophages from six cigarette smokers demonstrated higher random migration and greater chemotactic responsiveness to casein than did macrophages from seven nonsmokers. These observations are consistent with the concept that pulmonary macrophages are metabolically activated by cigarette smoking.     

Recurrent sepsis caused by Streptococcus pyogenes

I report that a 75-year-old man with severe atherosclerosis experienced two episodes of bacteremia with Streptococcus pyogenes of type emm87. Recurrent sepsis with S. pyogenes is extremely rare, and a foot ulcer was the suspected point of entry. The patient did not develop opsonizing antibodies to the isolate.     

Platelet aggregation by Streptococcus pyogenes.

Heat-killed group A Streptococcus pyogenes induced platelet aggregation in platelet-rich plasma. Aggregation was dependent upon the ratio of platelets to bacteria, with maximal aggregation occurring at 0.8 platelets per bacterium (final concentration, 300,000 per microliter). Inhibition of the reaction by 3 mM EDTA indicated it was a true aggregation and not merely adhesion and agglutination. Lactic acid dehydrogenase assays indicated lysis of platelets did not occur during a 6-min incubation period. Aggregation was inhibited in a dose-dependent manner by acetylsalicylic acid (100 microM to 10 mM) and quinacrine (15.6 to 250 microM), with no decrease in aggregation at the lowest concentration of inhibitor tested. S. pyogenes induced the release of [14C]serotonin, which was maximal (50%) at 2.4 min, when aggregation was nearly complete. Gel-filtered platelets were not aggregated unless fibrinogen (final concentration, 1.8 mg/ml) was included in the reaction mixture. Staphylococcus aureus, a group B streptococcus, and Escherichia coli were unable to induce aggregation in platelet-rich plasma under the conditions used for S. pyogenes.     

Expression of Fey Receptor-Mediated Phagocytosis by Airway Intra-Luminal Macrophages

Macrophages in the conducting airways of the lower respiratory tract constitute an anatomically defineable subpopulation of pulmonary macrophages. Little information regarding the functional characteristics of the airway intra-luminal macrophages (AI-LM) is currently available. In this study, the AI-LM resident in the trachea and mainstem bronchi of the rat were harvested by an airway lavage technique and the ability of the AI-LM to phagocytize by Fcy-receptors was evaluated relative to the phagocytic activities of alveolar macrophages (AM) obtained by bronchoalveolar lavage. More than 60% of the AI-LM phagocytized sheep erythrocytes opsonized with IgG (SRBC-IgG) and the distributions of the engulfed SRBC-IgG in the phagocytic AI-LM were virtually identical to those in AM. The AI-LM may represent AM that have been translocated from the alveolar space compartment to the conducting airways; it remains possible, however, that at least some of the AI-LM may have an airway origin. Regardless, the results of our phagocytic studies suggest AI-LM may functionally provide a protective phagocytic role in the conducting airways.     

Expression of Fey Receptor-Mediated Phagocytosis by Airway Intra-Luminal Macrophages

Macrophages in the conducting airways of the lower respiratory tract constitute an anatomically defineable subpopulation of pulmonary macrophages. Little information regarding the functional characteristics of the airway intra-luminal macrophages (AI-LM) is currently available. In this study, the AI-LM resident in the trachea and mainstem bronchi of the rat were harvested by an airway lavage technique and the ability of the AI-LM to phagocytize by Fcy-receptors was evaluated relative to the phagocytic activities of alveolar macrophages (AM) obtained by bronchoalveolar lavage. More than 60% of the AI-LM phagocytized sheep erythrocytes opsonized with IgG (SRBC-IgG) and the distributions of the engulfed SRBC-IgG in the phagocytic AI-LM were virtually identical to those in AM. The AI-LM may represent AM that have been translocated from the alveolar space compartment to the conducting airways; it remains possible, however, that at least some of the AI-LM may have an airway origin. Regardless, the results of our phagocytic studies suggest AI-LM may functionally provide a protective phagocytic role in the conducting airways.     

Interaction of Alveolar Macrophages with Nocardia asteroides: Immunological Enhancement of Phagocytosis, Phagosome-Lysosome Fusion, and Microbicidal Activity

Normal and specifically activated rabbit alveolar macrophages were infected in vitro with Nocardia asteroides GUH-2. In the presence of serum from normal rabbits, no significant differences were noted between normal and activated alveolar macrophages with respect to phagocytosis, incidence of phagosomelysosome fusion, or nocardicidal activity. However, all of these macrophage functions were enhanced by various immunological components. Serum from immunized rabbits enhanced phagocytosis of nocardial cells by activated macrophages, and there was an additional increase in phagocytosis observed when alveolar lining material was present. Complement had no effect on the ability of the macrophages to phagocytize nocardial cells. The greatest percentage of organisms phagocytized was observed when specifically primed lymph node cells, alveolar lining material, and serum from immunized rabbits were present in the incubation medium. N. asteroides GUH-2 inhibited phagosome-lysosome fusion in normal macrophages in the presence of serum from normal rabbits. However, addition of serum from immunized rabbits or the addition of specifically primed lymphocytes increased the amount of phagosome-lysosome fusion, whereas complement had no effect on this fusion process. Nocardial viability was not reduced when either normal or activated macrophages were infected with bacteria in the presence of normal serum, immune serum, or alveolar lining material. However, specifically activated macrophages incubated with primed lymph node cells obtained from immunized rabbits were able to both decrease the number of viable organisms recovered and to increase the incidence and extent of bacterial cell damage. The greatest number of organisms were killed by specifically activated macrophages when the bacterial cells were incubated with primed lymph node cells suspended in immune serum and alveolar lining material. These results indicate that activated macrophages alone are not sufficient to kill ingested N. asteroides GUH-2 and that specifically primed lymphocytes are important in host resistance to nocardial infections.     

In Vitro Migration of Human Alveolar Macrophages: Effects of Cigarette Smoking

The responsiveness of alveolar macrophages lavaged from healthy volunteers to migration inhibitory factor (MIF) was tested by using the capillary-tube assay method. In every instance, macrophages from nonsmokers responded to MIF as demonstrated by a depression in migration of at least 30%, whereas MIF did not inhibit migration of macrophages from smokers. Cells from smokers migrated at a rate three times faster than cells from nonsmokers. Migration of macrophages from nonsmokers with delayed hypersensitivity skin reactions to Candida albicans antigen was inhibited when antigen was present in the tissue culture medium. Antigen did not inhibit macrophages from subjects who lacked delayed hypersensitivity to the antigen, or from subjects who were cigarette smokers. Since alveolar macrophages can respond to MIF in vitro, they may play a role in cell-mediated immune reactions in the lung. Cigarette smoking may interfere with this participation.