Alveolar macrophage kinetics and multinucleated giant cell formation after lung injury

Abstract

Multinucleated giant cells (MGC) are a prominent feature of some chronic inflammatory states in the lung. These cells are formed by macrophage fusion, but how this process relates to the kinetics of alveolar macrophage (AM) production and proliferation is not clear. In this serial study, we compare AM kinetics and MGC formation after instilling carbon, silica, asbestos, bleomycin, and saline into the lungs of mice. Animals were killed up to 16 weeks later with [3H]thymidine injected 1 h before death. Counts of AM and MGC were carried out after bronchoalveolar lavage, and cell labeling was assessed by autoradiography. All test substances induced an inflammatory response with equal AM numbers recovered up to 2 weeks. Subsequently, the number returned to normal after carbon but remained elevated in the other groups. After carbon the lung structure was normal, there was no increase in AM label, and no MGC formed. Bleomycin-injected lungs progressed to fibrosis with only a brief, small increase in AM labeling and no MGC formation. After silica, and particularly asbestos, the lungs showed fibrosis, and many granulomas with large MGC were seen. Lavaged AM from these lungs showed a significant increase in DNA synthesis after 2 weeks, followed by higher numbers of MGC, none of which were labeled. Labeled AM tended to be free of particles, whereas MGC after 4 weeks contained many particles. The results indicate a relationship between AM proliferation and fusion, whereby AM growth appears to be prerequisite for cell infusion and MGC formation as a feature of granulomatous disease.

Obesity is associated with macrophage accumulation in adipose tissue

“…In the extremely obese animals, some of these macrophage aggregates completely surrounded adipocytes (Figure 2). These aggregates resembled the macrophage syncytia characteristic of chronic inflammatory states such as rheumatoid arthritis and foreign body giant cell induction (47)(48)(49).…”

Formyl Peptide Receptor-Like 2 Is Expressed and Functional in Plasmacytoid Dendritic Cells, Tissue-Specific Macrophage Subpopulations, and Eosinophils

“…Macrophages can also contribute to adaptive immunity by uptake and processing of Ags, thus triggering T lymphocyte responses. In the lung, alveolar macrophages play a crucial role of scavengers, keeping the alveoli clean and sterile (39). These properties distinguish them from other tissue macrophages, mainly involved in the processing and transfer of Ags to lymphoid receptors.…”

Monocyte and macrophage heterogeneity and Toll-like receptors in the lung

“…It is still not clear whether all of the lung macrophages are randomly derived from a specific monocyte pool following a specific inflammatory insult or whether each macrophage subpopulation has its specific lineage-committed precursor so that distinct populations are recruited in response to distinct stimuli and distinct locations. Furthermore, once macrophages reach the tissue, are they then terminally differentiated, or do they remain flexible in order to respond to different stimuli and to alter their phenotype and function according to changes in signals and microenvironment (Prieditis and Adamson 1996)? Accumulating evidence now indicates that monocytes are heterogeneous in several species and are themselves predetermined for particular functions in the steady state and inflammation.…”