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The Prolonged Life-Span of Alveolar Macrophages

¹ The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Jaime Murphy, M.D., The Pulmonary Center, R-304, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118. E-mail: murphj04{at}bu.edu

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 irradiation—however, 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.

Key Words: macrophages • half-life • PKH26

CLINICAL RELEVANCE We have developed a novel system for studying alveolar macrophages. The fact that these cells are much longer-lived than previously believed has significant impact on the interpretation and planning of studies related to alveolar macrophage biology.