The Prolonged Life-Span of Alveolar Macrophages

Abstract

To further examine the half-life of alveolar macrophages, chimeric CD 45.2 mice were generated through bone marrow transplantation of donor CD 45.1 cells. Before administration of donor cells, recipient mice were divided into two cohorts: the first cohort received total body irradiation; the second cohort also received irradiationhowever, the thorax, head, and upper extremities were shielded with lead. Flow cytometric analysis was then performed on blood, peritoneal, and bronchoalveolar lavage cells over time to quantify engraftment. The data generated for the unshielded cohort of mice revealed a macrophage half-life of 30 days. In the shielded cohort, however, we found that by 8 months there was negligible replacement of recipient alveolar macrophages by donor cells, despite reconstitution of the blood and peritoneum by donor bone marrow. Consistent with these findings, the mean fluorescent intensity of alveolar macrophages remained stable over a 4-week period after in vivo PKH26 dye loading. Together, these data show that previous alveolar macrophage half-life studies were confounded by the fact that they did not account for the toxic effects of irradiation conditioning regimens, and demonstrate that the bone marrow does not significantly contribute to the alveolar macrophage compartment during steady-state conditions.

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

“…Importantly, the Mreg characterized in our studies efficiently interferes with distinct inflammatory reactions after adoptive transfer and induces the production of IL-10 by CD4 + T cells in vivo, as well as in cultures of Ag-specific stimulated CD4 + T in vitro. Our findings are in line with several studies that demonstrate the longevity of macrophages and their immunosuppressive potential (22,23,41,42). Yet, to our knowledge, this is the first study to characterize a macrophage population induced by a single pathogen-derived immunomodulator that exerts immunosuppressive activities in unrelated inflammatory settings.…”

Fas Determines Differential Fates of Resident and Recruited Macrophages during Resolution of Acute Lung Injury

“…Other investigators have observed this result using radiation-limited bone marrow transplantation techniques that are complementary to ours (26)(27)(28). However, an inherent problem with bone marrow transplant techniques is that local replication cannot be excluded as a source for macrophage replacement.…”

Alveolar macrophages in pulmonary host defence – the unrecognized role of apoptosis as a mechanism of intracellular bacterial killing

“…Alveolar macrophages are very long-lived cells that may live for very prolonged periods in the steady state [10]. In murine models there was no detectable turnover and little local replication observed over 8 months, so in a steady state there may be only a limited requirement for in-situ replication because of intrinsic macrophage persistence.…”