The Origin of Alveolar Macrophages in Mouse Radiation Chimeras

Abstract

Most of the known bactericidal properties of the lungs reside in the phagocytic and lyric potential of the alveolar macrophages (1, 2). Besides maintaining the sterility of the alveolar surface, alveolar macrophages also participate in the clearance of dust and debris from the nonciliated portions of the lung (3, 4). As these important roles of the alveolar macrophage were recognized, m a n y investigators a t t e m p t e d to determine the origin of the cells (reviewed in Bertalanffy [5,6]).Several different cells have been suggested as the progenitor of the alveolar macrophage; the sources of macrophages most frequently mentioned have been hematopoietic tissues (7,8) and intrapulmonary tissues (9, 10). Recently, t'inkett et al. (11) utilized mouse irradiation chimeras in which donor hematopoiefic cells were marked by the T8 chromosome and concluded that two-thirds of alveolar macrophages were of hematopoiefic origin. Virolainen (12) applied the T6 method to organ culture and concluded that all dividing free cells were of hematopoietic origin. Unfortunately, the use of a chromosomal marker visible only during mitosis limited these studies to dividing cells and did not permit morphologic evaluation of these cells. Brunstetter et al. (13), using reciprocal chimeras in which donor hematopoietic cells either carried or lacked an identifiable esterase marker, concluded that alveolar macrophages were primarily of bone marrow origin. However, their analytical method was qualitative and necessitated the pooling of all free cells recovered in the lung washing.In view of these conflicting reports, it was apparent that the experimental approach to this problem must include: (a) a specific marker to identify the origin of individual alveolar macrophages, (b) the utilization of an unselected or randomly selected popu-* This paper has been presented in part at the

Lung Macrophages Serve as Obligatory Intermediate between Blood Monocytes and Alveolar Macrophages

“…Our finding, suggesting an indirect connection of blood monocytes and alveolar M⌽, agrees, for example, with the finding of Sawyer et al (25), showing that the alveolar M⌽ population is unaffected by experimentally induced blood monocyte depletion. Furthermore, the derivation of alveolar M⌽ from blood monocytes is in agreement with the previously reported replacement of these M⌽ by donor cells upon BM transfer (11,12), and the need for a lung intermediate can further explain the observed delayed reconstitution (13,14). Bowden and Adamson (23) suggested a dual origin for alveolar M⌽, either directly from blood-borne precursor or from local proliferation.…”

“…In addition, the alveolar M⌽ population was reported to remain unaffected by depletion of blood monocytes (25), leading to the conclusion that alveolar M⌽ are not monocyte derived (26). Because alveolar M⌽ are eventually replaced by BM-derived cells (11), the existence of circulating precursor was, however, not ruled out. Taken together, the identity of the alveolar M⌽ precursor, as well as its own origin, remains to be revealed (22).…”

“…Interestingly, however, after whole body irradiation and engraftment, their replacement by donor BM cells takes considerably longer than that of most other cells of the hematopoietic system (13,14). Depending on the irradiation protocol used, the time required for the complete exchange of alveolar M⌽ has been reported to vary from several weeks up to 1 year (11,(13)(14)(15)(16). This delay in alveolar M⌽ replacement by BM-derived cells is discussed as one of the critical causes for the sensitivity of BM transplantation patients to pulmonary infections (17,18).…”

“…Alveolar M⌽ are bone marrow (BM)-derived cells (11,12). Interestingly, however, after whole body irradiation and engraftment, their replacement by donor BM cells takes considerably longer than that of most other cells of the hematopoietic system (13,14).…”

Defective Phagocytosis and Clearance of Pseudomonas aeruginosa in the Lung Following Bone Marrow Transplantation

“…Neutropenia commonly results from myelosuppression induced by the conditioning regimen, delayed engraftment, or poor graft function. Failure of engraftment inevitably leads to mortality (23). However, infectious complications, specifically nosocomial pneumonias, significantly contribute to mortality after BMT even after hemopoietic engraftment has occurred.…”