Self-Renewal of Pulmonary Alveolar Macrophages: Evidence From Radiation Chimera Studies

Tarling, J. D.; Lin, Huawen; Hsu, Shin

doi:10.1002/jlb.42.5.443

Cited by 135 publications

(90 citation statements)

References 19 publications

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“…This population of cells is moderately resistant to ionizing irradiation [16] and likely represent a local lung progenitor cell for AMs. Using fractionated low-dose irradiation schemes, Tarling and colleagues demonstrated that when the AL-CFC population was not ablated, that AMs were repopulated by host cells; presumably the lung-resident AL-CFC [17]. However, high-dose irradiation schemes (>9 Gy) ablated the AL-CFC population and resulted in AM repopulation by donor BM cells [17].…”

Section: Discussionmentioning

confidence: 99%

“…Using fractionated low-dose irradiation schemes, Tarling and colleagues demonstrated that when the AL-CFC population was not ablated, that AMs were repopulated by host cells; presumably the lung-resident AL-CFC [17]. However, high-dose irradiation schemes (>9 Gy) ablated the AL-CFC population and resulted in AM repopulation by donor BM cells [17]. Our present results agree with these observations and confirm that 8 Gy TBI results in approximately 36% AM reconstitution from donor BM, whereas high-dose irradiation (13 Gy) results in ~80% AM repopulation from donor marrow.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Conditioning Regimens for Alveolar Macrophage Reconstitution and Innate Immune Function Post Bone Marrow Transplant

Hubbard

Ballinger

Wilke

et al. 2008

Experimental Lung Research

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The authors compared efficiency of alveolar macrophage (AM) reconstitution from donor bone marrow post transplant following 4 chemotherapy conditioning regimens and 2 total body irradiation (TBI) regimens. TBI regimens are more effective in inducing AM reconstitution from donor marrow. However, mice conditioned with 13 Gy split-dose TBI or a dual-chemotherapy regimen (25 mg/kg busulfan × 4 days plus cyclophosphamide 100 mg/kg × 2 days) both demonstrate significant AM repopulation from donor marrow. Additionally, both protocols resulted in impaired pulmonary host defense associated with overproduction of prostaglandin E 2 and I 2 by AMs and impaired AM phagocytosis post bone marrow transplant. Keywords phagocytosis; prostaglandin; P. aeruginosaThe lung has the largest interface with the outside environment of any internal organ in the body. As such, the lung is constantly bombarded with foreign particles and pathogens. Active host defense requires the orchestration of innate immune cells and immune mediators such as cytokines, chemokines, and eicosanoids to aid in the recognition, containment, and clearance of microorganisms [1]. Unfortunately, patients who have undergone stem cell transplantation are at risk for pulmonary infections [2][3][4][5] and pneumonia remains the leading infectious cause of death following stem cell transplantation despite the implementation of numerous prophylactic strategies and advances in diagnosis and treatment [6]. These transplant patients manifest increased susceptibility to infections for periods of time (months to years) post transplantation, extending long after engraftment of leukocytes from donor sources [2,7].We have previously established a murine model of gram-negative bacterial infection following bone marrow transplantation (BMT) and have shown that these mice are more susceptible to pulmonary infection with the gram-negative pathogen Pseudomonas aeruginosa due to defects in innate immune cells. these studies involved 13 Gy of total body irradiation (TBI) followed by reconstitution with 5 × 10 6 whole bone marrow (BM) cells + 1 × 10 6 syngeneic splenic T cells. We demonstrated that AMs from these mice were >87% donor-derived by 3 weeks post BMT [4]. Despite the fact that the alveolar macrophages (AMs) were largely donor derived, the AMs were defective in their ability to both phagocytose and kill bacteria [4,8]. In this model, AMs post BMT produced elevated amounts of prostaglandin E 2 (PGE 2 ), which is known to inhibit host defense [4,8,9]. However, one caveat to the extrapolation of these findings is that the experimental conditioning regimen utilized in our previous studies does not mimic human clinical practice. Thus, to determine the applicability of these findings to BMT performed following different conditioning regimens, we compared the level of AM reconstitution and prostaglandin production following multiple TBI and chemotherapy preparative regimens. Our results demonstrate that significant reconstitution of AMs from donor BM following either TBI or c...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparison of Conditioning Regimens for Alveolar Macrophage Reconstitution and Innate Immune Function Post Bone Marrow Transplant

Hubbard

Ballinger

Wilke

et al. 2008

Experimental Lung Research

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“…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).…”

mentioning

confidence: 99%

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

Landsman

Jung

2007

The Journal of Immunology

226

199

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Alveolar macrophages are a unique type of mononuclear phagocytes that populate the external surface of the lung cavity. Early studies have suggested that alveolar macrophages originate from tissue-resident, local precursors, whereas others reported their derivation from blood-borne cells. However, the role of circulating monocytes as precursors of alveolar macrophages was never directly tested. In this study, we show through the combined use of conditional cell ablation and adoptive cell transfer that alveolar macrophages originate in vivo from blood monocytes. Interestingly, this process requires an obligate intermediate stage, the differentiation of blood monocytes into parenchymal lung macrophages, which subsequently migrate into the alveolar space. We also provide direct evidence for the ability of both lung and alveolar macrophages to proliferate.

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“…, microglial cells [14], Langerhans cells [15], and alveolar macrophages [16,17] were shown to also proliferate locally. In contrast to those tissue macrophages, intestinal macrophages were reported to be nonproliferating [18].…”

mentioning

confidence: 99%

Intestinal macrophages: differentiation and involvement in intestinal immunopathologies

2009

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Intestinal macrophages, preferentially located in the subepithelial lamina propria, represent the largest pool of tissue macrophages in humans. As an adaptation to the local antigen-and bacteria-rich environment, intestinal macrophages exhibit several distinct phenotypic and functional characteristics. Notably, microbe-associated molecular pattern receptors, including the lipopolysaccharide (LPS) receptors CD14 and TLR4, and also the Fc receptors for IgA and IgG are absent on most intestinal macrophages under homeostatic conditions. Moreover, while macrophages in the intestinal mucosa are refractory to the induction of proinflammatory cytokine secretion, they still display potent phagocytic activity. These adaptations allow intestinal macrophages to comply with their main task, i.e., the efficient removal of microbes while maintaining local tissue homeostasis. In this paper, we review recent findings on the functional differentiation of monocyte subsets into distinct macrophage populations and on the phenotypic and functional adaptations that have evolved in intestinal macrophages in response to their antigen-rich environment. Furthermore, the involvement of intestinal macrophages in the pathogenesis of celiac disease and inflammatory bowel diseases is discussed.

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Self-Renewal of Pulmonary Alveolar Macrophages: Evidence From Radiation Chimera Studies

Cited by 135 publications

References 19 publications

Comparison of Conditioning Regimens for Alveolar Macrophage Reconstitution and Innate Immune Function Post Bone Marrow Transplant

Comparison of Conditioning Regimens for Alveolar Macrophage Reconstitution and Innate Immune Function Post Bone Marrow Transplant

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

Intestinal macrophages: differentiation and involvement in intestinal immunopathologies

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