Involvement of Granulocyte-Macrophage Colony-Stimulating Factor in Pulmonary Homeostasis

Dranoff, Glenn; Crawford, Alexander D.; Sadelain, Michel; Ream, Beverly; Rashid, Asif; Bronson, Roderick T.; Dickersin, G. Richard; Bachurski, Cindy J.; Mark, Eugene L.; Whitsett, Jeffrey A.; Mulligan, Richard C.

doi:10.1126/science.8171324

Cited by 824 publications

(611 citation statements)

References 35 publications

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“…delivery of a rBCG strain secreting detectable levels of GM-CSF in situ augments local immunogenicity and demonstrates significant protection against M. tuberculosis infection. GM-CSF is critical to the differentiation of myeloid cells such as DC and macrophages from haematopoietic stem cell precursors, yet in the lung it has been shown to possess unique functions in the regulation of inflammation and host defense against infectious pathogens, as well as pulmonary surfactant and alveolar cell homeostasis [23][24][25][26]. The pattern of GM-CSF production within the lung, with GM-CSF concentrations diminishing over time (Fig.…”

Section: Discussionmentioning

confidence: 99%

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

et al. 2009

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The rational design of new vaccines engineered to target key components of the host immune response is crucial to aid control of important infectious diseases such as tuberculosis. In this report, we determined whether modifying the function of pulmonary APC could improve protection against infection with Mycobacterium tuberculosis. Targeted delivery to the lung of the cytokine GM‐CSF, expressed by the Mycobacterium bovis BCG vaccine strain, increased pulmonary DC numbers and secretion of the immunoregulatory cytokine IL‐12, compared with parental BCG immunization. This impact on APC number by BCG:GM‐CSF resulted in accelerated priming of antigen‐specific CD4+ T cells in the mediastinal lymph nodes and increased migration of activated CD4+ T cells into the lung. i.n. administration of BCG:GM‐CSF resulted in significantly increased protection against M. tuberculosis infection compared with mice vaccinated with BCG alone. BCG:GM‐CSF exhibited an improved safety profile, as immunodeficient RAG1−/− mice vaccinated i.n. with BCG:GM‐CSF survived significantly longer than control BCG‐vaccinated mice. These data demonstrate that manipulating immune cells in the lung by BCG‐based delivery of GM‐CSF can assist the development of protective mucosal immunity against pulmonary bacterial infection.

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Section: Discussionmentioning

confidence: 99%

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

et al. 2009

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“…Dogs depleted of G-CSF by a neutralizing antibody develop profound and selective neutropenia [20], but dogs similarly depleted of GM-CSF do not become neutropenic [21]. Furthermore, disruption of the G-CSF gene in knock-out mice results in chronic neutropenia [22], whereas GM-CSF knock-out mice do not become neutropenic [23].…”

Section: Discussionmentioning

confidence: 99%

G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome

Aggarwal¹,

Cs²,

Evans³

et al. 2000

Eur Respir J

177

124

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Activated neutrophils play a major role in the pathogenesis of acute respiratory distress syndrome (ARDS), and persistence of pulmonary neutrophilia is related to poor survival. Interleukin (IL)‐8 is implicated in recruiting neutrophils to the lungs but it has been postulated that granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and granulocyte colony‐stimulating factor (G‐CSF), which can promote the survival of neutrophils by delaying apoptosis, may prolong the inflammatory response. The aim of this study was to investigate the levels of GM‐CSF and G‐CSF in the lungs of patients with ARDS and determine their relationship relative to IL‐8 with levels of neutrophils and clinical outcome. The lungs of 31 patients with ARDS were sampled by means of bronchoalveolar lavage (BAL) and assays of the three cytokines were conducted via enzyme‐linked immunosorbent assay. GM‐CSF, G‐CSF and IL‐8 were all increased in the patients compared to healthy controls but concentrations of GM‐CSF were much lower than those of G‐CSF and IL‐8 (GM‐CSF

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“…Although it has been suggested that most tissue macrophages are dependent on the cytokine macrophage-colony stimulating factor (M-CSF or Csf-1) for their development, there is now evidence that microglia and LCs can form in the absence of Csf-1 ligand (Ginhoux et al, 2006(Ginhoux et al, , 2010Kondo et al, 2007;Wegiel et al, 1998). In addition, the cytokine GM-CSF thought to control mostly DC development also controls lung alveolar macrophage function (Dranoff et al, 1994).…”

Section: Microglia and The Mononuclear Phagocyte Systemmentioning

confidence: 99%

Regulation of microglia development and homeostasis

Greter

Mérad

2012

Glia

116

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Microglia represent the resident macrophages of the central nervous system (CNS) and account for 10% of the adult glial cell population in the normal brain. Although microglial cells are thought to contribute to most pathological conditions including CNS infections, neuroinflammatory lesions, brain tumors, and neurodegenerative diseases, their exact role in CNS development, homeostasis, and disease remains poorly understood. In contrast to most macrophage populations, microglia survive high-dose ionizing radiation and maintain themselves locally and independently of circulating precursors in the steady state. However, controversies remain on the origin of microglia in the brain and whether they could potentially be repopulated by circulating myeloid precursors after brain injury. Microgliatargeted therapies through the use of genetically modified circulating hematopoietic cells proved to be a promising therapeutic strategy for the treatment of brain diseases. It is thus of great importance to understand the contribution and developmental cues of circulating myeloid cells as potential microglia progenitors to the adult pool of microglia in the steady state and under inflammatory conditions. V

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Involvement of Granulocyte-Macrophage Colony-Stimulating Factor in Pulmonary Homeostasis

Cited by 824 publications

References 35 publications

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome

Regulation of microglia development and homeostasis

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