Phagocytic Activity Of Alveolar Macrophages Research Articles

Stimulation of Phagocytic Activity of Alveolar Macrophages Toward Artificial Microspheres by Infection with Mycobacteria

The purpose of this study is to know the effect of uptake of mycobacteria on the phagocytic activity of alveolar macrophage (Mphi) cells toward poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with the anti-tuberculosis agent rifampicin (RFP-PLGA MS). Biological functions such as phagocytic activity toward PLGA MS loaded with fluorescent coumarin (cPLGA MS) and toward polystyrene latex MS (PSL MS), and generation of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) were examined using alveolar Mphi cell NR8383 after they had phagocytosed Mycobacterium bovis Calmette-Guérin (BCG), heat-killed BCG (h-kBCG) or Escherichia coli. The ingestion of BCG, h-kBCG, and E. coli did not affect the viability of the Mphi cells within 2 days. The phagocytosis caused generation of TNF-alpha and NO, being more significant with E. coli than with both types of BCGs. The phagocytosis of both types of BCGs stimulated the phagocytic uptake of cPLGA and PSL MS's, which took place prior to the generation of TNF-alpha or NO, but that of E. coli suppressed the uptake of both MS's. Mycobacterial infection stimulated the phagocytic uptake toward cPLGA MS. These results suggest that RFP-PLGA MS is favorable for overcoming tuberculosis.

Exact determination of phagocytic activity of alveolar macrophages toward polymer microspheres by elimination of those attached to the macrophage membrane

A method for exact determination of phagocytic activity of alveolar macrophage (Mϕ) cells toward synthetic microspheres (MS) by optical microscopy was developed. We examined the effectiveness of the treatment of Mϕ samples with trypsin, acid or xylene to remove the polystyrene latex microspheres (PSL MS) attached to Mϕ cell membranes during their phagocytosis by Mϕ cells. We found that centrifugation, which was employed to collect Mϕ samples after incubation with MS, affected significantly the efficiency of the various treatments. Of the three treatments, xylene treatment without centrifugation was the most effective to determine the phagocytic activity of Mϕ cells, as xylene dissolved the PSL MS on the cell surface almost completely. This treatment was also effective in the case of poly(lactic- co-glycolic acid) MS (PLGA MS), which have been commonly used as an efficient vehicle for drug delivery system.

Community-Acquired Pneumonia in Alcoholic Patients

In Brief Recent reports have identified alcoholism to have an important public health impact and cause a substantial loss of lives worldwide. For a long time alcoholism has been identified to favor pulmonary infections. But only in the last 2 decades the alterations induced by ethanol to the complex mechanisms of lung defense have been recognized. Alcohol alters lung defenses on all levels. It is known to favor oropharyngeal colonization by potentially pathogenic bacteria, aspiration by altering the cough reflex, and to decrease ciliary motility and surfactant production. Innate and adaptive immune responses on the systemic and alveolar level are compromised by alteration of cytokines, decreased chemotaxis, and phagocytic activity of alveolar macrophages and neutrophils. Recent data suggest that Streptococcus pneumoniae is the leading pathogen responsible for community-acquired pneumonia in alcoholic patients. However, series have reported Klebsiella pneumoniae, Legionella pneumophilia, and other Gram-negative enterobacteriaceae to be frequent, especially in severe cases. Anaerobes may play a role if aspiration after acute intoxication is the cause. The clinical course of community-acquired pneumonia in alcoholic patients is more severe leading to more intensive care unit care, longer hospital stay, and a delay of clinical improvement after initiation of therapy. Convincing data are available showing a predisposition of alcoholic patients for the development of acute respiratory distress syndrome. Some issues still remain controversial as to the rate of multiresistant bacteria or an increased mortality. Regarding the treatment of alcoholic patients, particularities and potential modifiers of antimicrobial treatment have to be accounted for. These include other frequent comorbid conditions such as chronic obstructive pulmonary disease and liver disease, complex socioeconomic and psychiatric conditions, and poor adherence to therapy. For a long time alcoholism has been identified to favor pulmonary infections. But only in the last 2 decades the alterations induced by ethanol to the complex mechanisms of lung defense been recognized. The following review provides an overview of the pathophysiology, epidemiology, and particular clinical aspects of community-acquired pneumonia in alcoholic patients.

Phagocytic activity of alveolar macrophages toward polystyrene latex microspheres and PLGA microspheres loaded with anti-tuberculosis agent

Phagocytosis of alveolar macrophages (Mϕs) toward poly(lactic- co-glycolic acid) (PLGA) microspheres (MS) loaded with the anti-tuberculosis agent rifampicin (RFP-PLGA MS) has been shown to be effective for the treatment of tuberculosis. The phagocytosis should be evaluated in terms of that toward reference MS. We chose polystyrene latex (PSL) MS as a reference. In this study, phagocytic activity of cell line NR8383, derived from rat alveolar Mϕ, toward PSL MS with various diameters was examined by incubating the cells for 4 h at 37 °C with various numbers of PSL MS per Mϕ cell (MS/Mϕ = 0.1–10). The results were then compared with those of the phagocytosis toward RFP-PLGA MS. We determined the phagocytic activity by counting the population of Mϕ cells that had phagocytosed MS ( N) and the number of particles phagocytosed ( n) in microscopic fields. Both N and n for PSL and RFP-PLGA MS increased in general with an increase in MS/Mϕ, but both of these values for PSL MS were smaller than those for RFP-PLGA MS. Phagocytosis of the particles were dependent on the particle size; i.e., of the PSL MS the 6-μm ones were taken up by Mϕ the most, and the RFP-PLGA MS 3 μm in diameter seemed to be phagocytosed the most efficiently, although we were not able to determine exactly the phagocytosis of 6- and 10-μm RFP-PLGA MS. From the changes in N and n values with MS/Mϕ, the phagocytosis of RFP-PLGA MS was likely to enhance the phagocytic activity of Mϕ cells, but this effect did not seem to be significant for PSL MS.

Optimum conditions for efficient phagocytosis of rifampicin-loaded PLGA microspheres by alveolar macrophages

We examined the phagocytic activities of alveolar macrophages (NR8383 cells) toward poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with the anti-tuberculosis agent rifampicin (RFP), the sizes of which were between 1 μm and 10 μm. We found that 1) the phagocytosis was dependent greatly on the particle size and the number of particles added; 2) macrophages phagocytosed considerably the PLGA microspheres loaded with RFP, the diameter of which was between 1 μm and 6 μm, but took up few 10-μm particles; 3) the population of the macrophages that phagocytosed 1-μm or 3-μm particles was larger than that of those phagocytosed 6- or 10-μm particles; 4) a considerable population of macrophages were not able to phagocytose even the 1- and 3-μm particles; 5) the most efficient deliveries of RFP into each macrophage cell and a large population of macrophages were achieved by the phagocytosis of 3-μm particles; and 6) phagocytosis did not affect macrophage viability in 4 h after the start of phagocytosis.

Early Neutrophil Recruitment and Aggregation in the Murine Lung Inhibit Germination ofAspergillus fumigatusConidia

Several types of polymorphonuclear neutrophil (PMN) deficiency are a predisposing condition for fatal Aspergillus fumigatus infection. In order to study the defensive role of PMNs in the lungs, with particular reference to PMN recruitment and antimicrobial oxidant activity, responses to pulmonary instillation of A. fumigatus conidia were examined. Responses in BALB/c and C57BL/6 mice were compared with those in CXCR2(-/-) and gp91(phox-/-) mice, which are known to have delayed recruitment of PMN to the lungs in response to inflammatory stimuli and inactive NADPH oxidase, respectively. In BALB/c mice, PMNs were recruited to the lungs and formed oxidase-active aggregates with conidia, which inhibited germination. In C57BL/6, gp91(phox-/-), and CXCR2(-/-) mice, PMN recruitment was slower and there was increased germination compared to that in BALB/c mice at 6 and 12 h. In gp91(phox-/-) mice, germination was extensive in PMN aggregates but negligible in alveolar macrophages (AM). Lung sections taken at 6 and 48 h from BALB/c mice showed PMN accumulation at peribronchiolar sites but no germinating conidia. Those from C57BL/6 and CXCR2(-/-) mice showed germinating conidia at 6 h but not at 48 h and few inflammatory cells. In contrast, those from gp91(phox-/-) mice showed germination at 6 h with more-extensive hyphal proliferation and tissue invasion at 48 h. These results indicate that when the lungs are exposed to large numbers of conidia, in addition to the phagocytic activity of AM, early PMN recruitment and formation of oxidative-active aggregates are essential in preventing germination of A. fumigatus conidia.

Suppression of Alveolar Macrophage Apoptosis Prolongs Survival of Rats and Mice withPneumocystisPneumonia

The number of alveolar macrophages is decreased in patients or animals with Pneumocystis pneumonia (Pcp). This loss of alveolar macrophages is in part due to apoptosis caused by Pneumocystis infection. The mechanism of apoptosis induction is unknown. Cell-free bronchoalveolar lavage fluids from Pneumocystis-infected rats or mice have the ability to induce apoptosis in normal alveolar macrophages. To characterize the mechanisms by which apoptosis proceeds in alveolar macrophages during Pcp, specific caspase inhibitors are tested for their ability to suppress the apoptosis. In vitro induction of apoptosis can be inhibited by the caspase-9 inhibitor (Z-LEHD-FMK) but not by the inhibitor to caspase-8 or -10. The caspase-9 inhibitor can also inhibit apoptosis of alveolar macrophages in vivo when it is intranasally instilled into dexamethasone-immunosuppressed, Pneumocystis-infected rats or L3T4 cell-depleted, Pneumocystis-infected mice. The number of alveolar macrophages rebounds in caspase-9 inhibitor-treated Pcp animals. Phagocytic activity of alveolar macrophages in treated animals is also recovered, and organism burden in these animals is reduced. Administration of caspase-9 inhibitor also clears the exudate that normally fills the alveoli during Pcp and decreases lung inflammation. Furthermore, caspase-9-treated Pcp animals survive for the entire 70-day period of the study, whereas nontreated Pcp animals die 40-60 days after initiation of infection. Depletion of recovered alveolar macrophages by intranasal administration of clodronate-containing liposomes in caspase-9 inhibitor-treated animals abrogates the effects of the inhibitor. Together, these results indicate that immunomodulation of the host response may be an alternative to current treatments for Pcp.

Surface tension influences cell shape and phagocytosis in alveolar macrophages

The effect of surface tension on alveolar macrophage shape and phagocytosis was assessed in vivo and in vitro. Surface tension was regulated in vivo by conditionally expressing surfactant protein (SP)-B in Sftpb-/- mice. Increased surface tension and respiratory distress were produced by depletion of SP-B and were readily reversed by repletion of SP-B in vivo. Electron microscopy was used to demonstrate that alveolar macrophages were usually located beneath the surfactant film on the alveolar surfaces. Reduction of SP-B increased surface tension and resulted in flattening of alveolar macrophages on epithelial surfaces in vivo. Phagocytosis of intratracheally injected fluorescent microbeads by alveolar macrophages was decreased during SP-B deficiency and was restored by repletion of SP-B in vivo. Incubation of MH-S cells, a mouse macrophage cell line, with inactive surfactant caused cell flattening and decreased phagocytosis in vitro, findings that were reversed by the addition of sheep surfactant or phospholipid containing SP-B. SP-B controls surface tension by forming a surfactant phospholipid film that regulates shape and nonspecific phagocytic activity of alveolar macrophages on the alveolar surface.

Lung cytotoxicity of combined exposure to refractory ceramic fibres and cigarette smoke.

Changes in some lung cytotoxic parameters after exposure to refractory ceramic fibres (RCF) or to cigarette smoke (S) and after combined exposure to RCF+S were studied in male Wistar rats in order to evaluate their potential adverse health effects. Four groups of rats were treated as follows : 1) intratracheally instilled by saline solution (0.4 ml); 2) intratracheally instilled by 4 mg of RCF; 3) exposed only to S (85 mg of total particulate matter/m(3) air ) for two hours daily; 4) exposed to RCF+S. After 6 months the animals were exsanguinated and the bronchoalveolar lavage (BAL) was perfomed. Viability and phagocytic activity of alveolar macrophages (AM), activity of lactate dehydrogenase (LDH) in cell-free BAL fluid (cf-BALF), acid phosphatase (ACP) and cathepsin D (CATD) in cfBALF, in BALF cells and in the lung tissue were estimated. Viability of AM was depressed by every type of exposure with RCF+S effect being at least additive. Phagocytic activity of AM increased in the presence of RCF. No significant changes in LDH activity were found. Activities of lysosomal enzymes measured in the lung tissue homogenates were not significantly changed, but those in the cfBALF increased especially after exposure to S with most expressive increase in BALF cells after exposure to S and RCF+S. In the case of CATD the effect of RCF+S was more than additive. The results point out to the persistence of the RCF exposure cytotoxic effects and their amplification by cigarette smoke.

Influence of refractory ceramic fibres - asbestos substitute - on the selected parameters of bronchoalveolar lavage 6 months after intratracheal instillation to W-rats

Industrial fibrous dusts are applied in many industrial branches and represent adverse factors in occupational and environmental area. Refractory ceramic fibers (RCFs) - amorphous alumina silicates - are used as one kind of asbestos substitutes. Because RCFs are relatively durable and some RCFs are respirable, they may present a potential health hazard by inhalation. The aim of present work was to find out the subchronic effect of RCFs on selected parameters of bronchoalveolar lavage (BAL) in W-rats, confirm the biopersistence of RCFs after 6 month instillation and contribute to the understanding of the pathomechanism of lung injury after fibrous dust exposure. Wistar rats were intratracheally instilled with 4 mg/animal of RCFs - exposed group and with 0.4 ml saline solution/animal - control group. Animals were sacrificed after 6 month exposure. Bronchoalveolar lavage (BAL) was performed and selected BAL parameters (mainly inflammatory and cytotoxic) were examined. After treatment with RCFs the following changes were observed: statistically significant increase in proportion of lymphocytes and polymorphonuclears as well as in % of immature alveolar macrophages (AM) and phagocytic activity of AM; statistically significant decrease in viability of AM and proportion of AM (from the differential cell count) in comparison with the control group. The results of this study indicated that RCFs even 6 months after intratracheal instillation very significantly changed the majority of examined BAL parameters. The presence of inflammatory and cytotoxic response in lung may signalize beginning or developing disease process.

HIV-1 Infection Does Not Impair Human Alveolar Macrophage Phagocytic Function Unless Combined With Cigarette Smoking

Macrophages are an important reservoir for the HIV and contribute to innate lung defense by their ability to phagocytose, digest, and process invading pathogens. We hypothesized that HIV-1 infection may lead to a defect in the phagocytic activity of alveolar macrophages. In order to test this hypothesis, the phagocytic activity of alveolar macrophages from asymptomatic HIV-1 seropositive subjects was compared to healthy seronegative control subjects. Macrophages from one cohort were fed with Escherichia coli and from another cohort with opsonized sheep RBCs (SRBCs), and the phagocytic index was determined at different time intervals. A tertiary-care, urban, university-based referral center. Asymptomatic HIV-1 seropositive subjects and healthy seropositive control subjects recruited from local community. No differences were found in the phagocytic activity between alveolar macrophages from the first cohort of eight seropositive and nine seronegative subjects. Although not statistically significant, there was a trend toward a lower phagocytic activity of HIV-positive smokers compared to HIV-positive nonsmokers. Opsonized phagocytic capacity (using opsonized SRBCs) was further analyzed in a second set of five HIV-positive subjects and five healthy control subjects. Whereas HIV status did not affect opsonized SRBC uptake, a history of smoking was associated with a statistically significant depression in phagocytic index. Although there is no significant impairment of phagocytic capacity in HIV-positive subjects compared to HIV-negative control subjects, cigarette smoking produces a significant depression in phagocytic activity that is amplified in HIV-positive smokers.

Pneumocystis carinii factor responsible for reduced phagocytic activity in alveolar macrophages.

Alveolar macrophages in hosts that are immunosuppressed and infected with Pneumocystis have a greatly reduced phagocytic activity [5]. Incubation of normal alveolar macrophages with bronchoalveolar lavage (BAL) fluid from P. carinii infected rats also leads to a decrease in phagocytosis [3]. The defect in phagocytosis has been linked to a down-regulation in transcription of the GATA-2 transcription factor [5]. Inhibition ofGATA-2 transcription in normal alveolarmacrophages leads to a reduction in phagocytic ability, and expression of GATA-2 in alveolar macrophages from P. carinii infected rats restores their phagocytic activity [5]. It is not known how P. carinii infection leads to down-regulation of GATA-2 or the decrease in phagocytosis. The current study represents the initial effort to identify factors from P. carinii responsible for the decrease in phagocytosis of alveolar macrophages.

Echinacea stimulates macrophage function in the lung and spleen of normal rats

Echinacea plant extract has been used for immunostimulation for many years but the evidence supporting its therapeutic potential is still controversial. Using male Sprague-Dawley rats (425–475 g), an in vivo study was conducted to examine the immunomodulatory effects of preparations of Echinacea containing its components cichoric acid, polysaccharides and alkylamides in different concentrations. The rats were gavaged orally with these preparations, two times/day for 4 days. Phagocytic activity of alveolar macrophage was increased with increasing concentrations of the Echinacea components. A trend of increase in TNF-α and nitric oxide release by the alveolar macrophages following an in vitro stimulation with LPS was also evident. An enhanced release of cytokines (such as TNF-α and IFN-γ) in response to Echinacea components, was also apparent in rat’s spleen macrophage, but at higher concentrations. These results suggest that the Echinacea preparations containing optimal concentrations of cichoric acid, polysaccharides and alkylamides are potentially effective in stimulating an in vivo, non-specific immune response in normal rats.

ICAM-1 facilitates alveolar macrophage phagocytic activity through effects on migration over the AEC surface.

We postulate that intercellular adhesion molecule-1 (ICAM-1) on type I alveolar epithelial cells (AEC) facilitates phagocytic activity of alveolar macrophages (AM) in the alveolus. When wild-type and ICAM-1-deficient mice were inoculated intratracheally with FITC-labeled microspheres, AM phagocytosis of beads (after 1 and 4 h) was significantly reduced in ICAM-1-/- mice compared with controls. To focus on ICAM-1-mediated interactions specifically involving AM and AEC, rat AM were placed in culture with rat AEC treated with neutralizing anti-ICAM-1 F(ab')(2) fragments. Blocking ICAM-1 significantly decreased the AM phagocytosis of beads. Planar chemotaxis of AM over the surface of AEC was also significantly impaired by neutralization of AEC ICAM-1. ICAM-1 in rat AEC is associated with the actin cytoskeleton. Planar chemotaxis of AM was also significantly reduced by pretreatment of the AEC monolayer with cytochalasin B to disrupt the actin cytoskeleton. These studies indicate that ICAM-1 on the AEC surface promotes mobility of AM in the alveolus and is critically important for the efficient phagocytosis of particulates by AM.

Lymphatic absorptive process of vitamin E and phagocytosis by alveolar macrophages in rats

The relationship between the absorption of vitamin E (VE) after intragastric administration and phagocytic activity of alveolar macrophages (AM) was examined using thoracic duct-cannulated rats. VE concentration in thoracic duct lymph fluid increased significantly in comparison to the control rats, and peaked 3 hr after administration of VE. The level of VE in the lung peaked 9 hr after administration, and was about two times higher than that of the control rats. After administration of VE, lipid droplets accumulated within the alveolar septa of the lungs. The levels of VE also peaked in bronchoalveolar lavage fluid (BALF) and in AM 9 hr after administration. Phagocytosis activity of IgG-opsonized-sheep red blood cells by AM gradually increased as the duration after administration increased. The activity of macrophage-activating factor (MAF) in BALF from rats administered VE also increased phagocytosis by AM from untreated rats. These results indicate that VE may directly affect the function of AM through activating MAF in the BALF of lungs after absorption from the thoracic duct without being metabolized in the liver.

Effect of Lactobacillus casei and Yogurt Administration on Prevention of Pseudomonas aeruginosa Infection in Young Mice

Pseudomonas aeruginosa is an opportunistic pathogen that rarely causes pulmonary disease in normal hosts but one that is an important cause of acute pneumonia in immunocompromised patients, including neonates, and of chronic pneumonia in patients with cystic fibrosis. The aim of this work was to study the effect of oral administration of Lactobacillus casei and yogurt on prevention of P. aeruginosa lung infection in young mice (3 weeks old). This study demonstrates that oral administration of L. casei or yogurt to young mice enhanced lung clearance of P. aeruginosa and phagocytic activity of alveolar macrophages through a dose-dependent effect. There were, however, no significant differences in white blood cell (WBC) differential counts. Furthermore, it was observed that previous administration of L. casei or yogurt induced a significant increase in IgA and IgM levels in bronchoalveolar lavages (BALs) after a P. aeruginosa infection, although there was no relationship with the serum values.

Inhibitory role of neutrophils on influenza virus multiplication in the lungs of mice.

The protective role of neutrophils on intranasal infection of influenza virus was investigated in 3 strains of tumor-bearing mice with neutrophilic leukocytosis. In vitro multiplication of influenza virus was inhibited by neutrophils from both normal and tumor-bearing mice, and the inhibitory effect of neutrophils was augmented by an addition of fMLP to the culture. Pulmonary virus infectivities in the early phase after infection decreased in such ICR and BALB/c mice, and virus elimination in the late phase was accelerated in the ICR mice. However, no decrease in pulmonary virus infectivity was observed in tumor-bearing C57BL/6 mice. Intranasal administration of fMLP into normal and tumor-bearing C57BL/6 mice after infection significantly inhibited the virus propagation in the lungs. The decrease in neutrophil infiltration into the lung in tumor-bearing C57BL/6 mice was confirmed from histological observations of the lung and lung lavage after infection and from analysis of the neutrophil chemotactic activity induced by fMLP. This might be responsible for the high level of pulmonary virus titer in tumor-bearing C57BL/6 mice. Phagocytic activities of alveolar macrophages and productions of neutralizing antibody were suppressed in the 3 strains of tumor-bearing mice. These observations indicated that neutrophils could be significant effector cells as a host defense mechanism against influenza virus infection in vivo, and infiltration and functional activation of neutrophils could play a significant role in virus elimination from the infected site. Furthermore, the inhibition of virus propagation by neutrophils in vitro was almost completely abrogated by an addition of ZnSO4, suggesting that calprotectin could inhibit influenza virus multiplication.

Effect of the Transcription Factor GATA‐2 on Phagocytic Activity of Alveolar Macrophages from Pneumocystis carinii‐Infected Hosts

Effect of the Transcription Factor GATA‐2 on Phagocytic Activity of Alveolar Macrophages from Pneumocystis carinii‐Infected Hosts

Avaliação da função de macrófagos alveolares em cavalos clinicamente sadios

Devido à importância dos macrófagos alveolares (MA) nos mecanismos de defesa pulmonar, foram realizados estudos para avaliar a atividade desses fagócitos em cavalos hígidos. Foram realizados lavados broncoalveolares (LBA) em cinco cavalos clinicamente sadios. A citologia foi realizada pela citocentrifugação das amostras e posterior confecção de lâminas coradas pelo método de Rosenfeld. Todas as amostras do LBA foram centrifugadas e a concentração celular foi ajustada para 2×10(6) células/ml, para a mensuração da atividade macrofágica (testes de espraiamento, fagocitose e liberação de peróxido de hidrogênio). A contagem diferencial das células presentes no LBA demonstrou a predominância de macrófagos (59,0± 6,9%). Os resultados obtidos nos testes de mensuração da atividade macrofágica foram: índice de espraiamento 25,1± 19,7%, índice de fagocitose 89,4± 6,2% e liberação de peróxido de hidrogênio 1,6± 0,3nmoles/2×10(5) células (sem PMA - phorbol 12-myristate 13-acetate) e 1,8± 0,4nmoles/2×10(5) células (com PMA). Os resultados demonstraram um padrão de atividade para MA de cavalos hígidos, os quais apresentaram índices de ativação mesmo sem elicitação prévia, indicando que as técnicas utilizadas foram adequadas para tal propósito.

Functional Activity of Alveolar and Peripheral Cells in Patients with Human Acquired Immunodeficiency Syndrome and Pulmonary Tuberculosis

We compared the peripheral and pulmonary response to assess the phagocytic activity of monocytes/macrophages and neutrophils and the lymphoproliferative response (LPR) againstMycobacterium tuberculosisantigens from 21 AIDS patients, presenting at diagnosis with active pulmonary tuberculosis (TB), other non-TB pulmonary infection, or no pulmonary infection, as well as patients with active pulmonary TB and healthy control subjects. Alveolar lymphocyte analysis demonstrated that AIDS/TB patients had more markedly reduced percentages of CD4+lymphocytes than AIDS/TB patients and an increase in the percentage of CD8+lymphocytes, probably reflecting the impairment of CD4+T lymphocytes in peripheral blood at the lungs. Moreover, alveolar lymphocytes from AIDS/TB patients demonstrated a two- to fourfold decrease in LPR againstM. tuberculosisantigens. Interestingly, it was observed an enhanced migration of natural killer cells to the lungs in all patients group. The phagocytic activity in alveolar macrophages and neutrophils showed that AIDS/TB patients had a twofold decreased capacity to ingest inert particles compared with AIDS patients. Comparing the alveolar and peripheral lymphocyte number and functional activity toM. tuberculosis-antigens it was possible to demonstrate that in both sites these cells had similar profile. However, the innate immune response in lungs showed a reduced activation in the presence of HIV infection, regarding theM. tuberculosiscoinfection. These findings suggest that the advanced impairment of CD4+T lymphocyte in HIV-1 infection may lead to a deactivation of alveolar macrophages, enhancing bacilli burden and HIV replication in the lungs and furthering dissemination.