The Role of the Alveolar Macrophage in the Clearance of Bacteria From the Lung

Abstract

PLATES 6 AND 7(Received for publication, July 29, 1963) Inhaled bacteria disappear rapidly from the lungs of experimental animals (1-3). This early clearance of bacteria is thought to be an important process in non-specific resistance to infection in the bronchopulmonary tree. Quantitative methods of study have provided a sensitive tool for detecting small as well as large changes in the efficiency of these mechanisms of resistance. A wide variety of chemical, hormonal, and environmental agents depress, :to different degrees, the rate at which inhaled cultivable bacteria disappear from the lungs (4). Such studies support epidemiologic evidence that multiple agents may be involved in the pathogenesis of chronic infections It is not clear to what extent each of the several component defense systems of the bronchopulmonary tree participates in the initial inactivation of inhaled bacteria. Although the mucociliary stream is frequently credited with this cleansing action, indirect evidence suggests that bacterial clearance may be accomplished by alveolar macrophages. In an attempt to answer this question directly, the pathway through the lung followed by inhaled bacteria was first traced by bacterial localization studies using conventional histologic and immunofluorescence methods. The latter method was used to localize bacterial antigen where the structural integrity of the organism had been destroyed. Then, radio-labeled viable bacteria were used to compare the rate at which inhaled bacteria lose their viability with the rate at which they are physically removed from lung tissue. In this way the action of bactericidal mechanisms such as phagocytosis was compared with the action of removal mechanisms such as the mucociliary stream and lymphatic drainage. The results of both studies point to the phagocytic action of macrophages as the major mechanism of early resistance to bacterial infection.

Host Airway Proteins Interact withStaphylococcus aureusduring Early Pneumonia

“…The identification of proteins such as Rab7, Rab11B, and syntenin suggests that S. aureus is present in late endosomes; these three proteins are specific to late phagosomes that are preparing to fuse with lysosomes in the phagosome maturation process (8,45). These data, combined with our data showing that S. aureus is rapidly associated with or internalized by AMs and PMNs in the airway, provide additional evidence to support the findings of previous studies demonstrating that the phagocytosis of S. aureus occurs quickly (13,23,28) and is followed by the survival of the bacteria within the phagocytes (15).…”

“…Nearly 80% of the proteins we identified were intracellular proteins, suggesting that S. aureus was rapidly internalized in the airway and that S. aureus infection caused rapid host cell lysis, presumably as a result of apoptosis, necrosis, or S. aureus toxin activity. S. aureus has previously been shown to be phagocytosed by AMs as rapidly as 30 min postinoculation in an aerosolization model (13,23,28); thus, it is not surprising that we detected a large number of phagosomal proteins associated with S. aureus 30 min and 6 h postinoculation. In fact, of the 404 intracellular proteins, 105 of them have previously been shown to be components of the phagosomal proteome of macrophages and/or PMNs (3,11).…”

Effect of Polycyclic Aromatic Hydrocarbons and Carbon Black Particles on Pro-Inflammatory Cytokine Secretion: Impact of PAH Coating Onto Particles

“…Alveolar macrophages (AM) are primarily responsible for clearance of inhaled particles and bacteria in the lung (Green and Kass, 1964;Warheit and Hartsky, 1993). They are considered a key cellular component in pulmonary innate immunity (Laskin and Laskin, 2001) as well as inflammatoryrelated pathologies (Barnes, 2004).…”

RESISTANCE TO KLEBSIELLA PNEVMONIAE AND THE IMPORTANCE OF TWO BACTERIAL ANTIGENS

“…1976). The most important cellular components of immunity represented in the lungs appear to be the alveolar macrophages which arc said to be responsible for maintaining the sterility of the lower respiratory tract (Green and Kass, 1964).…”