Introduction
Due to differences in their anatomical locations, ontogenies (development and formation), developmental pathways, gene expression patterns, and immunological functions, macrophages found in different tissue types are all unique. As the first line of defense for the respiratory tract, Alveolar macrophages (AMs) are found in the alveolar lumen of the lungs. Numerous pulmonary diseases, including pulmonary alveolar proteinosis (PAP, a rare lung disorder caused by the accumulation of proteins, fats, and other materials in the alveoli), allergic asthma, Chronic Obstructive Pulmonary Disease (COPD), viral infection, and bacterial infection, are associated with the immunological functions of AMs. Thus, extensive research has been done on the molecular mechanisms underlying the development and function of alveolar macrophages.
What Are Alveolar Macrophages?
Alveolar macrophages are a type of white blood cells. They are also referred to as dust cells. Cellular and humoral immune system components are separated. Protecting the alveoli from respiratory pathogen invasion begins with alveolar macrophages. Close to pneumocytes, they are found in pulmonary alveoli and the inter-alveolar septum. Gas exchange occurs in the alveoli, the respiratory system's terminal unit. Three different types of cells make up the alveoli:
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Type I Pneumocytes: They contribute to the alveolar wall's structure and support respiration. They do not multiply or divide.
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Surfactants: They are a type of lipoprotein secreted by type II pneumocytes that prevents the alveoli from collapsing even after exhalation.
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Different Signaling Substances: They are made by alveolar macrophages that interact with other immune system cells to coordinate a response that keeps the bodies immunologic and tissue homeostasis. Type II pneumocytes replenish both types of pneumocytes and AMs, and these cells are essential for tissue remodeling and host defenses.
How Are Alveolar Macrophages Formed?
The hematopoietic stem cells (primitive cells that develop into all types of blood cells) made in the bone marrow from the common myeloid progenitor (precursors of red blood cells and platelets) are the source of all mononuclear phagocyte cell types. The myeloblasts produced by these myeloid cells later differentiate into monocytes. In the organ's connective tissue, monocytes mature into macrophages after traveling through the bloodstream. Even before monocytes are present, alveolar macrophages can exist in the tissue. Macrophages can survive in the tissue for months or years, while monocytes only have a day-long half-life. Alveolar macrophages can differ in size and shape from person to person based on the phagocytic function and the cell's environment in the body. The activation of the microtubule network during phagocytosis or mobilization allows the cell membranes of the alveolar macrophages to change shape. Chemotaxis is the term used to describe the movement of alveolar macrophages in response to specific chemicals at the site of tissue injury. Chemotaxis and endocytosis (the process by which substances are brought into the cells) are facilitated by the unique actin microfilament structure of alveolar macrophages.
What Are the Functions of Alveolar Macrophages?
Scavenging micro-organisms like viruses, bacteria, fungi, tissue debris, inhaled environmental particles like coal, silica, asbestos, and cancer cells is a significant function of the alveolar macrophages. Toll-like Receptors (TLR) on the surface of alveolar macrophages engage with pathogen-associated molecular receptors (PAMP) on the microbial cell to activate the macrophages. The interaction between PAMPs and TLRs sends chemical signals that start the pathogen engulfment process and cause pro-inflammatory cytokines to be secreted, which strengthens the immune response locally. Phagosomes (vesicles created around substances that phagocytose into cells) and lysosomes combine during phagocytosis to generate phagolysosomes, which release digestive enzymes that eliminate the infection. Some bacteria, like Mycobacterium tuberculosis, are resistant to phagocytosis. Alveolar macrophages stop the infection in such situations before it spreads to the other organs. Macrophages can take up specific environmental particles, such as silica and carbon, and ingest them to keep them out of circulation. Pro-inflammatory cytokines are involved in tissue healing and fibrosis during an active inflammatory response.
The alveolar macrophages live in the alveolar spaces under homeostatic conditions. When the respiratory tract is exposed to different external stimuli, AMs use efferocytosis to show anti-inflammatory action in the alveolar spaces. Compared to macrophages from healthy individuals, those from patients with severe COPD or asthma exhibit weak phagocytic capacity. Patients with respiratory disorders may experience persistent inflammation due to this discrepancy.
In addition, AMs contribute to immunosuppression by encouraging the production of regulatory T (Treg) cells. Treg cells encourage the development of monocytes into macrophages that resemble AMs in laryngeal squamous cell carcinoma, which shows that there is a positive feedback loop between AM and Treg cell formation. The alveolar microenvironment actively contributes to ongoing signaling that encourages AM immunosuppressive behavior.
AMs can switch to execute various pro-inflammatory actions despite their immunosuppressive role in non-inflammatory alveolar areas. Immunosuppressive AMs become pro-inflammatory when the epithelial cells in the airway are destroyed, and immunosuppressive ligands are lost as a result. In acute lung damage models, neutrophil extracellular traps cause AMs to become inflamed, indicating that AMs can be stimulated to play various pro-inflammatory roles through different methods. AMs show increased phagocytic activity and release of pro-inflammatory cytokines and oxygen metabolites after changing into a pro-inflammatory state. Depending on the characteristics of the alveolar microenvironment, AMs can have pro-inflammatory and immunosuppressive effects. While the immunosuppressive activity of the AM is constantly encouraged by non-inflammatory alveolar microenvironments, inflammatory alveolar microenvironments cause AMs to engage in pro-inflammatory activities. Therefore, increasing our knowledge of the dual roles played by AMs in a variety of lung disorders may aid in the discovery of new and potent drug targets.
What Is the Clinical Significance of Alveolar Macrophages?
The Bronchoalveolar Lavage (BAL), which is taken from the lungs of smokers and COPD (chronic obstructive pulmonary disorder) patients, has more alveolar macrophages. It was discovered that smokers have four to six times higher levels of macrophage when compared to nonsmokers. Aside from this, smokers' alveolar macrophages differ morphologically from non-smokers' and have more free radicals and toxic pigment. The chronic lung disease emphysema is brought on by the elastases released by neutrophils, which break down terminal airways. Remarkably, smokers' lavage also contains significant levels of elastases as alveolar macrophages secrete them. In Interstitial Pulmonary Fibrosis (IPF), lung tissue is replaced by fibrotic tissue; alveolar macrophages play a role in this disorder. Fibroblasts are present in the BAL fluid of individuals with IPF but are missing from healthy lung tissue.
Conclusion
AMs are important immune cells that live in the alveoli. They are always on the lookout for threats to the homeostasis there. Respiratory infections and outside stimulation are constant threats to the human lungs. There is a dearth of research analyzing the connections between AM metabolic status and development and function, even though the major soluble variables influencing AM development and function are largely known.
