Role of Pulmonary Macrophages in Resistance to Experimental Metastasis

Jackson, Ronnie A.; Lill, Patsy H.; Gangemi, J. David

doi:10.1002/jlb.40.5.575

Cited by 7 publications

(2 citation statements)

References 8 publications

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“…Furthermore, pulmonary macrophages activated by intranasal inoculation of Propionibacterium acnes failed to reduce metastases of fibrosarcoma cells injected i.v. (35). These studies were intriguing but were devoid of modern-day understanding and technical advancement to finely characterize or identify the precise role of AM.…”

Section: Am In Metastasismentioning

confidence: 99%

Pulmonary Alveolar Macrophages Contribute to the Premetastatic Niche by Suppressing Antitumor T Cell Responses in the Lungs

Sharma

Chintala

Vadrevu

et al. 2015

The Journal of Immunology

135

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In contrast to tumor-associated macrophages, myeloid-derived suppressor cells, or inflammatory monocytes, functions of tissue resident macrophages, including alveolar macrophages (AM), in cancer were not well studied. Using a mouse model of breast cancer, we show that AM promote cancer metastasis to the lungs by suppressing antitumor T cells in this organ. AM accumulated in the premetastatic lungs through complement C5a receptor–mediated proliferation but not through recruitment from the circulation. AM preconditioned by breast tumors inhibited Th1 and favored generation of Th2 cells that had lower tumoricidal activity than Th1 cells. In addition, AM reduced the number and maturation of lung dendritic cells by regulating TGF-β in the lung environment. Depletion of AM reversed immunosuppression imposed by these cells and strengthened local Th1 responses, which significantly reduced lung metastatic burden. C5a receptor deficiency, which also lessens myeloid-derived suppressor cells in the premetastatic niche, synergized with the depletion of AM in preventing metastasis, leading to protection of mice from lung metastases. This study identifies AM as a new component of the premetastatic niche, which is harnessed by tumors to impose immunosuppression, and as a new target for cancer immunotherapies to eliminate or reduce metastasis. Because the lungs are the most common target for hematogenous metastasis, this research offers a plausible explanation for susceptibility of the lungs to cancer metastasis.

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Section: Am In Metastasismentioning

confidence: 99%

Pulmonary Alveolar Macrophages Contribute to the Premetastatic Niche by Suppressing Antitumor T Cell Responses in the Lungs

Sharma

Chintala

Vadrevu

et al. 2015

The Journal of Immunology

135

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“…It is possible that other molecular patterns found on E. chaffeensis interact with Tlr4. The Tlr4 gene not only regulates macrophage responsiveness to LPS, but also appears to regulate responsiveness to a number of substances including, Propionibacterium acnes (Jackson et al, 1986), calcium ionophore (Perera et al, 1996; Shinomiya and Nakano, 1987), taxol (Perera et al, 1996; Shinomiya and Nakano, 1987), and staphylococcal exoproteins (Chapes and Beharka, 1995; Fleming et al, 1991). Thus, the LPS Tlr4-d/d genotype (mutant) has wide ranging consequences which may impact the host response to several pathogens.…”

Section: Manipulating Immune Response Genes To Understand Ehrlichia Rmentioning

confidence: 99%

Defining the immune response to Ehrlichia species using murine models

Chapes

Ganta

2008

Veterinary Parasitology

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Pathogenic bacteria belonging to the family Anaplasmataceae include species of the genera Ehrlichia and Anaplasma. Ehrlichia chaffeensis, first known as the causative agent of human monocytic ehrlichiosis, also infects several vertebrate hosts including white-tailed deer, dogs, coyotes and goats. E. chaffeensis is transmitted from the bite of an infected hard tick, such as Amblyomma americanum. E. chaffeensis and other tick-transmitted pathogens have adapted to both the tick and vertebrate host cell environments. Although E. chaffeensis persists in both vertebrate and tick hosts for long periods of time, little is known about that process. Immunological studies will be valuable in assessing how the pathogen persists in nature in both vertebrate and invertebrate hosts. Understanding the host immune response to the pathogen originating from dual host backgrounds is also important to develop effective methods of diagnosis, control and treatment. In this paper, we provide our perspective of the current understanding of the immune response against E. chaffeensis in relation to other related Anaplasmataceae pathogens. E. chaffeensis belongs to the Anaplasmatacease familyThe family Anaplasmataceae contains several species of obligate, intracellular, Gram-negative bacteria which include species of the genera Ehrlichia and Anaplasma (Dumler et al., 2001;Ristic and Huxsoll, 1984). A steady increase of potentially fatal human diseases caused by Ehrlichia and Anaplasma species that infect phagocytic cells has been reported in recent years (Dumler and Bakken, 1995;McDade, 1990;Schaffner and Standaert, 1996). These include human monocytic ehrlichiosis (HME) caused by the tick-transmitted rickettsial, Ehrlichia chaffeensis (Chen et al., 1997;Dawson et al., 1991;Maeda et al., 1987;Paddock et al., 1997), human granulocytic ehrlichiosis caused by Ehrlichia ewingii (Buller et al., 1999) and human granulocytic anaplasmosis (HGA) caused by Anaplasma phagocytophilum (Chen et al., 1994). Ehrlichia canis and Ehrlichia (Cowdria) ruminantium are responsible for causing canine monocytic ehrlichiosis and heartwater in dogs and ruminants, respectively (Kock et al., 1995;Perez et al., 1996;Perreau et al., 1980;Uilenberg, 1983). E. canis has also been reported to cause infections in people in Venezuela (Perez et al., 1996 and. E. canis has a worldwide distribution except Australia, while E. ruminantium is distributed in all parts of the sub-Saharan Africa and in the Caribbean (McDade, 1990;Rikihisa, 1991;Uilenberg, 1983).Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Using m...

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Tumoricidal Activity of Alveolar and Peritoneal Macrophages of C57BL/6 Mice Bearing Metastatic or Nonmetastatic Variants of Lewis Lung Carcinoma

Duffie

Young

1991

Journal of Leukocyte Biology

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The spontaneous tumoricidal abilities of alveolar and peritoneal macrophages from C57B1/6 mice bearing a metastatic or a nonmetastatic cloned variant of Lewis lung carcinoma (LLC) were measured. Cytotoxicity by alveolar macrophages was enhanced during the first few weeks after subcutaneous (s.c.) or intravenous (i.v.) injection of metastatic LLC-C3 cells, but not after injection of nonmetastatic LLC-C8 cells. Alveolar macrophages from mice with s.c.-injected metastatic tumors, but not with nonmetastatic tumors, could be further activated in vitro, but not beyond the maximal level of spontaneous cytotoxicity. Late in tumor growth, the spontaneous cytotoxicity by alveolar macrophages of metastatic LLC-C3 tumor bearers was suppressed and could not be increased by in vitro activation. The tumoricidal abilities of peritoneal macrophages from mice bearing either LLC-C3 or LLC-C8 tumors were modulated in a similar way, as were alveolar macrophages. The reduced cytotoxicity by alveolar macrophages from mice with nonmetastatic tumors or from mice bearing large metastatic tumors was not due to suppression by macrophage-derived prostaglandins. The loss of tumoricidal capabilities by macrophages from mice with large metastatic LLC-C3 tumors was not caused by elevated systemic prostaglandin E2 (PGE2) levels. These results suggest that alveolar and peritoneal macrophages are activated to be cytotoxic during development of pulmonary metastases and do not need to be functionally depressed for successful establishment of metastases.

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Role of Pulmonary Macrophages in Resistance to Experimental Metastasis

Cited by 7 publications

References 8 publications

Pulmonary Alveolar Macrophages Contribute to the Premetastatic Niche by Suppressing Antitumor T Cell Responses in the Lungs

Pulmonary Alveolar Macrophages Contribute to the Premetastatic Niche by Suppressing Antitumor T Cell Responses in the Lungs

Defining the immune response to Ehrlichia species using murine models

Tumoricidal Activity of Alveolar and Peritoneal Macrophages of C57BL/6 Mice Bearing Metastatic or Nonmetastatic Variants of Lewis Lung Carcinoma

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