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Activation of neutrophils by lipid A, O-antigen polysaccharides (PS) and smooth lipopolysaccharides (LPS) isolated from Salmonella choleraesuis (O-6,7) and Salmonella typhimurium (0-4,5,12) was investigated. The methods used were assays for lysozyme release and for nitroblue tetrazolium (NBT) reduction which measures the level of oxidative metabolism of neutrophils. LPS from both species stimulated neutrophils to the same extent in the presence of autologous plasma. In the absence of plasma only the O-6,7 LPS activated neutrophils. Lipid A or PS isolated from both LPS either did not activate neutrophils or did so only at very high concentrations when tested in the presence of plasma; in the absence of plasma no activation occurred. The data indicate that both PS and lipid A segments of LPS are required for activation of neutrophils by LPS. We also deduce that plasma, probably complement, is required for the interaction of some LPS, e.g. O-4,5,12 with neutrophils whereas other LPS, e.g. O-6,7 can interact directly and activate neutrophils. [ABSTRACT FROM AUTHOR]

Alveolar macrophages (AMs) from 12 healthy volunteers were loaded with small masses of ultrafine carbon particle aggregates. Their phagocytic activity was studied 20 h after the loading. We used three different fluorescein-labelled test particles. Silica particles (3.2 µm) were studied with four different carbon concentrations from 0.03 to 3 µg/106 AMs. Heat-killed Candida albicans (3.8 µm) and Cryptococcus neoformans (6.1 µm) opsonized with specific IgG were studied at 1 µg carbon /10 6 AMs. Both the attachment and ingestion processes were studied. The ingested carbon induced a dose-related impairment of both the attachment and the ingestion of silica particles and a significant impairment down to a carbon load of 0.2 µg/106 AMs. Also, the phagocytosis of C. neoformans and C. albicans by AMs was impaired by the carbon load. Small carbon loads thus impaired phagocytosis of three different particles which attach to different AM receptors: scavenger receptors (silica particles), mannose receptors (C. albicans) and Fc receptors (C. neoformans). Ambient air particles, at an episode of high particle concentration, may thus impair the phagocytic capacity of AMs and this might increase the risk for lung infections in patients with severe lung and heart diseases. [ABSTRACT FROM AUTHOR]

We hypothesized that aggregates of ultrafine carbon and washed diesel particles impair the ability of alveolar macrophages (AM) to kill bacteria and enhance the AM lipid peroxidation (LPO) of lung surfactant. Rat AM were exposed, 5h, to particles 20 microg/ml. The AM, containing carbon or washed diesel particles, were incubated 2h, with Streptococcus pneumoniae, an American Type Culture Collection (ATCC) strain or clinical isolates. Surviving bacteria were quantified. Surfactant was incubated, 5h, with carbon or washed diesel loaded AM and LPO was measured. The particle load was approximately 1 microg/10(6) AM, representing accepted exposure to ambient particles in Europe. Metal concentrations were 10 to 100 fold higher in washed diesel--than in carbon particles. There was a dose dependent increase in bacterial survival with carbon-loaded macrophages, but not with washed diesel-loaded AM. Clinical isolates had a higher survival rate with carbon-loaded macrophages than the ATCC strain. Surfactant LPO was increased with washed diesel-loaded macrophages (95%) and with carbon-loaded macrophages (55%) compared to controls. High LPO caused by washed diesel-loaded AM reflects their increased oxidative metabolism, probably caused by particle metals. The additional oxygen metabolites maintained bactericidal activity of AM, while corresponding activity was decreased in carbon-loaded AM. Altered functions of AM may explain health problems related to air pollution.

We investigated whether exposure of alveolar macrophages to aggregates of ultrafine carbon particles affected subsequent phagocytosis of microorganisms. Human alveolar macrophages were obtained by bronchoalveolar lavage and exposed to aggregates of ultrafine carbon particles or diesel exhaust particles (DEP) for 20 h before measurements of phagocytosis. The particle loads were estimated to be comparable to those of air pollution exposure with established health effects in humans. Phagocytotic activity was measured as attachment and ingestion of four different test particles (amorphous silica particles, yeast cells from Candida albicans, and Cryptococcus neoformans opsonized with specific IgG or fresh serum) that bind to scavenger, mannose, Fc, and complement receptors, respectively. Carbon preloading significantly impaired the attachment and ingestion process (P<0.01) for all particles, except for yeast cells from C. neoformans opsonized with specific IgG. On the average, the accumulated attachment decreased by 30% and the ingested fraction decreased by 10%. Loading of alveolar macrophages with either aggregates of ultrafine DEP or carbon particles impaired the phagocytosis of silica test particles in a similar way. Exposure of human alveolar macrophages to aggregates of carbon or DEP, in concentrations relevant to human environmental exposures, caused significant impairment of phagocytosis of silica particles and microorganisms. The inhibitory effect on particle phagocytosis mediated by four different receptors suggests that air pollution particles cause a general inhibition of macrophage phagocytosis. Such an effect may contribute to increased susceptibility to infections and, for example, result in more exacerbations of asthma and chronic obstructive pulmonary disease.

In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation. Preterm rabbits (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg radiolabeled surfactant (14C-Curosurf) and randomized to 4 h of spontaneous breathing or mechanical ventilation or to a control group, killed immediately after surfactant administration. With pharyngeal deposition, 46 +/- 10% (mean +/- SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax compliance was higher in spontaneously breathing compared with mechanically ventilated animals (median, 9.9 and 0.75 ml x cm H2O(-1) x kg(-1), respectively; p < 0.05). The relative distribution of 14C-Curosurf in bronchoalveolar lavage fluid and homogenized lung tissue showed a higher degree of tissue association in the spontaneously breathing animals [53 +/- 4 versus 26 +/- 3% (mean +/- SEM)] than in mechanically ventilated animals (p < 0.01), the latter figure being very similar to that of the control group (25 +/- 5%). There was a higher degree of lipid peroxidation and fewer microbubbles in bronchoalveolar lavage fluid from mechanically ventilated animals. We conclude that the initial lung tissue association of exogenous surfactant is impaired by mechanical ventilation. This is associated with a reduction of dynamic compliance and evidence of increased surfactant inactivation.

Partial liquid ventilation (PLV) with perfluorocarbons has been considered as an alternative therapy for severe inflammatory lung disease. The present study was performed to test whether PLV influences bacterial growth and lung histology in a rabbit model of congenital pneumonia caused by group B streptococci. Near-term newborn rabbits were tracheotomized, inoculated via the airways with group B streptococci, and subsequently ventilated for 5 h with either PLV or conventional ventilation. At 30 min after group B streptococci administration, animals in the PLV group (n = 16) received 30 mL/kg body weight of perfluorocarbon (PF 5080) via the tracheal tube. Evaporative losses were substituted with 20 mL/kg perfluorocarbon at hourly intervals. Identical volumes of air were injected in control animals at the same times (n = 15). The number of colony-forming units in left lung homogenate, evaluated at the end of the experiments, tended to be lower in PLV-treated animals than in controls (6.8 x 109 versus 6.4 x 1010 colony-forming units/g body weight; p = 0.06). Comparison of these numbers with the colony-forming units injected at the beginning of the experiments revealed a reduction in bacterial number in the PLV group and proliferation in the controls (-2.2 x 108 versus +5.6 x 1010 colony-forming units/g body weight; p < 0.05). Histologic examination demonstrated less inflammation and more homogeneous lung expansion in PLV-treated animals. Two animals in the PLV group had focal interstitial emphysema. Our results suggest that PLV with PF 5080 reduces bacterial proliferation in experimental group B streptococcal pneumonia.

Phagocytosis of three types of fluorescein-labeled test particles by rat alveolar macrophages (AM) were studied: spherical silica (3.2 microm), heat-killed Candida albicans (3.8 microm), and heat-killed Cryptococcus neoformans (6.1 microm) opsonized with specific IgG. These particles should attach to scavenger, mannose, and Fc receptors, respectively. Both control AM and AM pretreated for 20 h with interferon-gamma (12.5 or 50 U/ml) were studied. The sum of the number of attached and ingested particles per AM (accumulated attachment) was used as a measure of the attachment process, and the number of ingested particles per AM divided by the accumulated attachment (ingested fraction) was used as a measure of the ingestion process. The average ingestion time (IT), which is also a measure of the ingestion process, was calculated from the experimental data. The ingestion process was independent of the attachment process. IT increased with the time of observation. This is explained by the fact that IT determined from observation times shorter than the whole distribution of IT for a certain particle results in a shorter IT than the real average IT. C. albicans (mannose receptor) had the fastest ingestion process, C. neoformans opsonized with specific IgG (Fc receptor) had ingestion that was nearly as fast, and the silica particles (scavenger receptors) had the slowest ingestion process. Treatment with interferon-gamma markedly impaired the attachment process for all three types of particles (and three types of receptors) but clearly impaired the ingestion process only for silica particles (scavenger receptors).

Objective: To investigate the effect of surfactant and specific antibody on bacterial proliferation in experimental pneumococcal pneumonia., Methods: Near-term newborn rabbits received a standard dose (10(7)) of type 3 pneumococci via the airways. Control animals were sacrificed 1 minute later. Other animals were ventilated for 5 hours and treated via the tracheal cannula with surfactant (Curosurf 200 mg/kg), a mixture of surfactant and a polyclonal antipneumococcal antibody, the antibody without surfactant, or saline., Results: There was a significant bacterial proliferation in lung tissue in all animals ventilated for 5 hours. Bacterial growth, expressed as log10 colony forming units (CFU) per gram of lung tissue was less prominent in animals treated with a mixture of surfactant and specific antibody than in animals treated with antibody alone (median, 7.51, range, 6.80--7.70 vs. median, 7.92, range, 7.07--8.50; P < 0.05). Dynamic lung-thorax compliance was improved with surfactant or surfactant plus antibody in comparison with saline or antibody alone., Conclusions: The data suggest that the suppressive effect of the antibody on bacterial proliferation becomes evident only when surfactant is administered together with the antibody.

Neonates suffering from group B streptococcal (GBS) pneumonia often lack type-specific opsonizing antibodies. We studied the influence of combined intratracheal treatment with surfactant and a specific antibacterial polyclonal antibody (IgG fraction) on bacterial proliferation and lung function in an animal model of GBS pneumonia. Near-term newborn rabbits received an intratracheal injection of either the specific IgG antibody, nonspecific IgG, surfactant, a mixture of surfactant and the antibody, or 0.9% saline. At 30 min the rabbits were infected with a standard dose (10(8)) of the encapsulated GBS strain 090 Ia. After 5 h of mechanical ventilation the mean estimated increase in bacterial number in lung homogenate (log10 colonies/g) was 0.76 in the antibody group, 0.92 in the nonspecific IgG group, 0.55 in the surfactant group, and 1.29 in the saline group. A mean decrease in bacterial number (-0.05) was observed in the group that received combined treatment with surfactant and antibody (p < 0.05 versus all other groups). Lung-thorax compliance was significantly higher in both groups of surfactant-treated animals compared with saline or IgG treatment. We conclude that in experimental neonatal GBS pneumonia combined treatment with surfactant and a specific immunoglobulin against GBS reduced bacterial proliferation more effectively than either treatment alone.

In vitro interaction of human alveolar macrophages (AM) with heat-killed conidia from Aspergillus fumigatus and inert silica particles of similar size, about 3 microns, was studied. The conidia were phagocytized significantly faster by AM than were the control particles partly due to the faster rate of attachment but especially due to the faster rate of ingestion. Quantitative nitroblue tetrazolium (NBT) reduction by AM, reflecting their release of oxygen radicals, was increased by a factor of 2 to 3 in response to the conidia during phagocytosis. The silica particles induced a moderate but significant increase in NBT reduction. Conidia, but not silica particles, showed a considerable percentage (around 8%) of phagolysosomes with neutral pH after 3 h and a smaller percentage (around 1%) after 24 h of incubation. The pH of phagolysosomes with conidia tended to be higher after 3 h, but was significantly lower after 24 h than the pH of phagolysosomes with silica particles. Despite the markedly increased oxidative metabolism there was no increase in cytokine production [interleukins (IL) 6 and 8 and tumor necrosis factor alpha (TNF-alpha)] after exposure to conidia. The silica particles induced a significant decrease in IL-6 and IL-8 production and a tendency toward decreased production of TNF-alpha. The occurrence of phagolysosomes with neutral pH suggests unsealed phagolysosomes from which not only oxygen metabolites but also enzymes might escape from the cell. Lung damage may thus be the result of repeated or long-term exposure to Aspergillus conidia.

In vitro interaction of alveolar macrophages (AM) from rats with conidia from Aspergillus fumigatus and Aspergillus candidus as well as inert control particles (amorphous silica) of similar diameter (about 3 microns), was studied. Experimental observations showed that both kinds of conidia were phagocytized significantly faster by AM than were the control particles due to a faster rate of attachment, but even more so due to a faster rate of ingestion. Quantitative nitroblue tetrazolium reduction by AM reflecting their oxidative metabolism and oxygen radical release was increased in response to both kinds of conidia by a factor of 2-3 during the process of phagocytosis, as well as 24 hr after the onset of phagocytosis, compared to corresponding conditions with inert particles and to resting macrophages. The mean pH in phagolysosomes with each of the conidia tended to be higher after 3 hr but was significantly lower after 24 hr than in the phagolysosomes with the control particles. After 3 hr there was a considerable percentage (around 8%) of phagolysosomes with pH > or = 6.5 and after 24 hr there was still a small percentage (0.7%) of such phagolysosomes for each of the conidia. Such a fraction was not observed for the control particles. Electron microscopic studies showed passages between phagolysosomes and AM surface with both kinds of conidia. The occurrence of such unsealed phagolysosomes might explain the percentage of phagolysosomes with high pH. Hence, Aspergillus conidia in unsealed macrophage vacuoles mediate an increased oxygen radical release from the macrophages, a process which in the long run might cause lung damage.

We studied bacterial proliferation in relation to surfactant treatment in a model of neonatal group B streptococcal (GBS) pneumonia. Surfactant (Curosurf) was isolated from pig lungs with a method preserving only polar lipids and hydrophobic proteins. Near-term rabbit fetuses were ventilated in a body plethysmograph system. At 15 min, a suspension of GBS strain 090 Ia LD (5 mL/kg, concentration approximately 10(9)/mL) was instilled intratracheally. At 30 min, surfactant (n = 12) or sterile saline (n = 13) was administered via the airways (2.5 mL/kg). A control group (n = 12) received the same volumes of saline. After 5 h the animals were killed, and samples for blood cultures and blood gases were taken from the heart. The left lung was aseptically removed, weighed, homogenized, serially diluted, and cultured on blood agar plates. The results were expressed as mean log10 colony forming units/g lung +/- SD. Compared with animals (n = 12) killed immediately after GBS instillation (8.13 +/- 0.54), there was a significant increase in bacterial numbers in both groups ventilated for 5 h, but values for surfactant-treated animals (8.96 +/- 0.38) were lower than those for animals receiving saline (9.46 +/- 0.50; p < 0.05). After 5 h, 96% of GBS-infected animals had positive blood cultures. Light microscopic examination of the right lung of GBS-infected animals revealed inflammatory changes that tended to be less prominent in surfactant-treated rabbits. We conclude that intratracheal inoculation of near-term rabbits with GBS resulted in a significant bacterial proliferation during 5 h of ventilation and that bacterial growth was mitigated by treatment with surfactant.

Activation of neutrophils by lipid A, O-antigen polysaccharides (PS) and smooth lipopolysaccharides (LPS) isolated from Salmonella choleraesuis (O-6,7) and Salmonella typhimurium (O-4,5,12) was investigated. The methods used were assays for lysozyme release and for nitroblue tetrazolium (NBT) reduction which measures the level of oxidative metabolism of neutrophils. LPS from both species stimulated neutrophils to the same extent in the presence of autologous plasma. In the absence of plasma only the O-6,7 LPS activated neutrophils. Lipid A or PS isolated from both LPS either did not activate neutrophils or did so only at very high concentrations when tested in the presence of plasma; in the absence of plasma no activation occurred. The data indicate that both PS and lipid A segments of LPS are required for activation of neutrophils by LPS. We also deduce that plasma, probably complement, is required for the interaction of some LPS, e.g. O-4,5,12 with neutrophils whereas other LPS, e.g. O-6,7 can interact directly and activate neutrophils.

Groups of eight rabbits were inhalation-exposed to iron, 1.4 +/- 0.7 mg/m3 (low Fe), or 3.1 +/- 1.8 mg/m3 (high Fe) as FeCl3 or to filtered air (controls) for 2 months, 5 days/week and 6 hours/day. The alveolar macrophages were increased in number in both exposed groups. Noduli of granular macrophages were found in lungs of all the rabbits in the high-Fe group, in one from the low-Fe group, and in one control rabbit. Especially in the high-Fe group there were prominent changes in the macrophages such as enlarged lysosomes containing fibrous-looking structures, iron-rich inclusions, and densely packed, 5-nm electron-dense granules. The number of cells filled with surfactant-like inclusions as well as a smooth surface was increased in the high-Fe group and the macrophages had enhanced phagocytic capacity. There was an increase in the phospholipid concentration and in the volume density of type II cells in the high-Fe group but the level of phosphatidylcholines was not significantly changed. The fact that Fe3+ affected mainly the alveolar macrophages might be due to the relatively high concentration of iron in these cells caused by the precipitation of iron in their lysosomes.

Eight rabbits were exposed to 0.7 +/- 0.4 mg/m3 Co2+ as CoCl2 and 1.2 +/- 0.7 mg/m3 Cr3+ as Cr(NO3)3 (group Co + Cr), eight to 0.6 +/- 0.5 mg/m3 Co2+ (group Co), and eight to filtered air (control group), for 4 months, 5 days/week, and 6 hr/day. All rabbits in group Co + Cr and group Co showed nodular aggregation of alveolar epithelial type II cells. Volume density of the type II cells was significantly higher in group Co + Cr than in group Co and the control group. There was intraalveolar macrophage accumulation in seven rabbits in group Co + Cr, one in group Co, and one in the control group. In lavage fluid the numbers of macrophages and the percentage of these cells with smooth surface and intracellular surfactant-like inclusions were more increased in group Co + Cr than in group Co as were oxidative metabolic and phagocytic activities of the macrophages. Total phospholipids, phosphatidylcholines, and especially 1,2-dipalmitoylphosphatidylcholine was markedly increased in group Co + Cr whereas only 1,2-dipalmitoylphosphatidylcholine was slightly increased in group Co. One mechanism behind the high amount of surfactant phospholipids in group Co + Cr seems to be an enhanced production of surfactant by the type II cells. Another mechanism is probably that Cr3+ reduces the capacity of alveolar macrophages to catabolize surfactant. The results imply that it is important to investigate effects of combinations of cobalt and chromium in the occupational environment.

For 4 and 8 months (5 days/week, 6 hr/day) rabbits were exposed to 0.13 +/- 0.05 (mean +/- SD) mg/m3 of metallic nickel dust. Volume density of alveolar type II cells was estimated with electron microscopy. Lavaged alveolar macrophages were studied with light and electron microscopy and their abilities to reduce nitroblue tetrazolium (NBT) and to phagocytize particles were tested. The effects seemed to be similar after 4 and 8 months of exposure and when the exposed animals were combined, volume density of type II cells was increased and also significantly correlated with concentration of disaturated phosphatidylcholines in the lung. The macrophages had an active surface. Their NBT activity at rest was increased but a further increase during stimulation with E. coli was low, suggesting an impaired function. Phagocytic activity, however, was not significantly changed.

Rabbits were exposed to aerosols of MnCl2 (mass median aerodynamic diameter 1 micron) in metal concentrations of 1.1 and 3.9 mg/m3 for 4-6 weeks, 5 days/week, 6 h/day. The effects of alveolar type II cells, phospholipids, alveolar macrophages, and lung structure in general were compared with earlier reported effects of Ni2+, Cd2+, Cu2+, and Co2+. Except for a significant increase in the diameter of the alveolar macrophages after exposure to the higher Mn2+ concentration, no abnormalities were seen. The results of this and earlier studies indicate that these five metal ions have different, specific effects on the alveolar part of the lung.

Rabbits were exposed to a combination of 0.7 mg/m3 Ni2+ as NiCl2 and 1.2 mg/m3 of Cr3+ as Cr(NO3)3, to 0.6 mg/m3 of Ni2+ as NiCl2, or to filtered air for about 4 months, 5 days/week and 6 hr/day. Alveolar macrophages were recovered by lung lavage and studied by light and electron microscopy. Metabolic activity, phagocytic capacity and lysozyme activity in the macrophages were studied. After the combined exposure, the effects on lung weight, number of macrophages, and appearance of surface and number of intracellular laminated inclusions in these cells were more than additive. These effects might be explained by a combination of increased production by Ni2+ and impaired catabolism of surfactant by Cr3+. Because the metal concentrations used were not far above occupational threshold limit values, combined exposures to nickel and trivalent chromium should be considered more seriously.

The in vitro influence of interferon (IFN) on various functions of human neutrophilic granulocytes was investigated. It was observed that the attachment and engulfment of opsonized yeast particles by human neutrophilic granulocytes were enhanced after preincubation in vitro with IFN for 30 min. The same result was obtained whether the particles were opsonized with fresh normal serum (complement) or with specific antibodies. However, after incubation of the granulocytes with IFN for 3 h the phagocytosis rate was somewhat decreased. Nitroblue tetrazolium (NBT) reduction by resting granulocytes was slightly, although not significantly, increased by preincubation with IFN for 30 min, but their NBT reduction during phagocytosis of E. coli was significantly increased. No major effects of preincubation with IFN were observed on spontaneous or random migration of granulocytes.

Rabbits were exposed to 0.6 mg/m3 of nickel as NiCl2 for about one month. After exposure, alveolar macrophages were lavaged from the lung and divided into three fractions by elutriation. Laminated structures in the macrophages were related to fraction number so that the fractions with the largest cells contained the highest number of structures. The lysozyme activity decreased in unfractionated as well as in fractionated macrophages from nickel exposed rabbits. The decrease was most pronounced in the fraction with the smallest macrophages and smallest number of laminated structures. Therefore the pronounced decrease in lysozyme activity seen in this and earlier studies is not caused by the increased amount of surfactant material. Increased amount of surfactant is a hallmark of nickel inhalation exposure and the surfactant material is responsible for the morphological and metabolic effects of the macrophages. The decreased lysozyme activity is probably a direct effect of nickel on the macrophages.

Rabbits were exposed to aerosols of chlorides of cadmium, copper, and cobalt (0.4-0.6 mg/m3 as metal) for 1 month (5 days/weeks and 6 hr/day). The effects of alveolar macrophages were compared with earlier reported effects of nickel chloride (0.3 mg/m3 as Ni). Effects of Cd2+ exposure resembled those of Ni2+ exposure. The number of macrophages in lavage fluid and the variance of cell diameters were thus increased and many cells contained lamellated inclusions. Contrary to macrophages from Ni2+-exposed rabbits, the surface of about 50% of the cells had cytoplasmic blebs. However, such cells were rarely seen by scanning electron microscopy. There were significantly more polymorphonucleated neutrophils and small lymphocytes, suggesting lung parenchymal damage. Cells from Cd2+-exposed animals, like cells from Ni2+-exposed ones, showed an increased oxidative metabolic activity after stimulation with Escherichia coli bacteria. Bactericidal capacity, on the other hand, tended to be enhanced rather than decreased, as in the nickel experiment. After CO2+ exposure, the number of macrophages was slightly increased in the lavage fluid and the cells showed an increased metabolic activity both at rest and upon stimulation with bacteria. Cu2+ exposure gave a slight increase in lamellated inclusions in the macrophages.

Rabbits were exposed to 2 or 0.4 mg/m3 of cobalt as CoCl2 for 14-16 weeks (5 days/week and 6 hr/day). More macrophages were lavaged from the lungs of rabbits exposed to the higher Co2+ concentration, and the diameter and variation of the diameter of the macrophages were significantly larger than in controls. The activity of lysozyme in the lavage fluid and in the macrophages was increased in the two exposed groups. Some macrophages in the exposed animals were large and engorged with intracellular lamellar inclusions and lipid droplets. Most of these cells had a smooth surface. The oxidative metabolic activity measured by reduction of nitroblue tetrazolium was increased in the exposed groups. The number of yeast cell particles attached to the surface of the macrophages was increased in the group exposed to the high concentration, but the number of ingested particles was not affected by cobalt exposure. Apart from the fact cobalt increased lysozyme activity whereas nickel decreased it, cobalt produced the same type of effects on macrophages as nickel did in earlier studies. Cobalt affected only a minor proportion whereas nickel affected most macrophages. This can be explained by the fact nickel produced a general increase in the volume density of the type II cells while cobalt affected the type II cells only in some areas of the lungs.

The influence of daily intramuscular injections of 3 X 10(6) units of interferon-alpha (IFN-alpha) on the phagocytic activity of peripheral monocytes was studied in 28 tumor patients. One day after initiation of IFN therapy no major change in the capacity of monocytes to ingest yeast particles was observed. After 1 week, 3 months, 6 months, and 9 months of treatment, monocyte phagocytosis had decreased in the majority of the patients tested. In patients where natural killer (NK) cell activity was measured simultaneously with monocyte phagocytosis, a correlation between the degree of enhancement of NK activity and the degree of decrease in monocyte phagocytosis was observed.

Alveolar macrophages from eight rabbits, exposed for about 1 month (5 days/week, 6 hr/day) to an aerosol of nickel chloride, 0.3 mg/m3 (as Ni), were studied. The number of macrophages in the lavage fluid and the variance of the cell diameter increased. The macrophages contained laminated structures and most cells had an active cell surface. A few macrophages had a large number of laminated structures and a smooth cell surface. The capacity of the macrophages to reduce nitroblue tetrazolium (NBT) tended to be increased at rest and was significantly increased after stimulation with Escherichia coli. The bactericidal capacity of the macrophages was decreased. The effects were similar to those earlier described after exposure of rabbits for 1 month to about 1 mg/m3 of metallic nickel dust. After exposure both to metallic and soluble nickel the effects are probably caused by an increased amount of surfactant produced by the type II cells in response to nickel ions.

Rabbits inhaled aerosols of hexavalent chromium (Na2CrO4) and trivalent chromium (Cr(NO3)3) at concentrations of 0.9 and 0.6 mg/m3 of the metal, respectively, for 4-6 weeks (5 days/week and 6 hr/day). Significantly more macrophages were obtained from the lungs of rabbits exposed to Cr(VI) but not from rabbits exposed to Cr(III) as compared with the controls. Macrophages from rabbits exposed to Cr(III) showed several conspicuous changes. About one-third of the macrophages contained round dark inclusions, 0.5-1.5 micron diameter, rich in chromium. Most cells had very large lysosomes which contained membranous fragments of different sizes surrounded by a more homogeneous matrix. Laminated inclusions similar to the lamellar bodies in the type II cells increased in number as did the percentage of cells with a smooth cell surface. Also macrophages from rabbits exposed to Cr(VI) showed morphological changes. The most pronounced one was enlarged lysosomes which contained short lamellae and electron-dense patchy inclusions. Only Cr(III) produced functional changes of the macrophages. The metabolic activity measured by reduction of nitroblue tetrazolium was increased and the phagocytic activity reduced.