Antibody-Dependent Cellular Cytotoxicity off Blood Monocytes and Alveolar Macrophages in Patients with Lung Cancer

Human peripheral blood monocytes were isolated by counterflow centrifugation elutriation (CCE). This technique was modified in such a way that various monocyte fractions (viability greater than 99%) could be elutriated by increasing the density of the CCE-medium in steps of 0.0027 g/ml. All monocytes showed the same size distributions as determined by electronic sizing, which indicated that they differed in their density only. Both cytoplasmic esterase and peroxidase activity increased with the density of the cells. Furthermore, the monocytes with the highest density were 2.3–4 times more active in an antibody- dependent cellular cytotoxicity (ADCC) assay than those with the lowest density. In contrast, the monocyte with the highest density were less capable to induce the proliferation of lymphocytes in mixed leukocyte cultures (MLC) than those with the lowest density. This observation could not be attributed to differences in the expression of HLA-DR determinants, since a monoclonal antibody directed against HLA-DR antigens reacted equally well with the monocytes in different fractions. These results provide evidence for the existence of functionally different subsets of monocytes or different states of differentiation or maturation.

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Chimeric and humanized anti-HM1.24 antibodies mediate antibody-dependent cellular cytotoxicity against lung cancer cells

Lung Cancer ◽

10.1016/j.lungcan.2008.04.009 ◽

2009 ◽

Vol 63 (1) ◽

pp. 23-31 ◽

Cited By ~ 14

Author(s):

Wei Wang ◽

Yasuhiko Nishioka ◽

Shuji Ozaki ◽

Ali Jalili ◽

Vinod Kumar Verma ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Lung Cancer Cells ◽

Cellular Cytotoxicity ◽

Antibody Dependent Cellular Cytotoxicity

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Isolation of functionally different human monocytes by counterflow centrifugation elutriation

Blood ◽

10.1182/blood.v60.1.46.46 ◽

1982 ◽

Vol 60 (1) ◽

pp. 46-53 ◽

Cited By ~ 73

Author(s):

CG Figdor ◽

WS Bont ◽

I Touw ◽

J de Roos ◽

EE Roosnek ◽

...

Keyword(s):

Human Peripheral Blood ◽

Size Distributions ◽

Cellular Cytotoxicity ◽

Human Monocytes ◽

Antibody Dependent Cellular Cytotoxicity ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Hla Dr ◽

Adcc Assay ◽

Proliferation Of Lymphocytes

Abstract Human peripheral blood monocytes were isolated by counterflow centrifugation elutriation (CCE). This technique was modified in such a way that various monocyte fractions (viability greater than 99%) could be elutriated by increasing the density of the CCE-medium in steps of 0.0027 g/ml. All monocytes showed the same size distributions as determined by electronic sizing, which indicated that they differed in their density only. Both cytoplasmic esterase and peroxidase activity increased with the density of the cells. Furthermore, the monocytes with the highest density were 2.3–4 times more active in an antibody- dependent cellular cytotoxicity (ADCC) assay than those with the lowest density. In contrast, the monocyte with the highest density were less capable to induce the proliferation of lymphocytes in mixed leukocyte cultures (MLC) than those with the lowest density. This observation could not be attributed to differences in the expression of HLA-DR determinants, since a monoclonal antibody directed against HLA-DR antigens reacted equally well with the monocytes in different fractions. These results provide evidence for the existence of functionally different subsets of monocytes or different states of differentiation or maturation.

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CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes

Scientific Reports ◽

10.1038/srep34310 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 60

Author(s):

Wei Hseun Yeap ◽

Kok Loon Wong ◽

Noriko Shimasaki ◽

Esmeralda Chi Yuan Teo ◽

Jeffrey Kim Siang Quek ◽

...

Keyword(s):

Leukemic Cells ◽

Target Cells ◽

Cellular Cytotoxicity ◽

Antibody Dependent Cellular Cytotoxicity ◽

Blood Monocytes ◽

Tlr Agonists ◽

B Virus ◽

Cd16 Expression ◽

Infected Cells ◽

Cytokine Stimulation

Abstract Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16− expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated β2-integrins and induced TNFα secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFα-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNγ, further enhanced ADCC. Monocytes lacking CD16 did not exert ADCC but acquired this property after CD16 expression was induced by either cytokine stimulation or transient transfection. Notably, CD16+ monocytes from patients with leukemia also exerted potent ADCC. Hence, CD16+ monocytes are important effectors of ADCC, suggesting further developments of this property in the context of cellular therapies for cancer and infectious diseases.

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Chemiluminescence and Antibody-dependent, Cell-mediated Cytotoxicity between Human Alveolar Macrophages and Peripheral Blood Monocytes in Smokers, Nonsmokers, and Lung Cancer Patients

CHEST Journal ◽

10.1378/chest.95.3.553 ◽

1989 ◽

Vol 95 (3) ◽

pp. 553-557 ◽

Cited By ~ 7

Author(s):

Ching-Chi Lin ◽

Wen-Chu Huang ◽

Ching-Yuang Lin

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Alveolar Macrophages ◽

Peripheral Blood ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Lung Cancer Patients ◽

Human Alveolar Macrophages ◽

Dependent Cell

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Effects of Cytokines on Oxygen Radical Production by Peripheral Blood Monocytes and Alveolar Macrophages in Patients with Lung Cancer

Tumori Journal ◽

10.1177/030089169608200417 ◽

1996 ◽

Vol 82 (4) ◽

pp. 382-385 ◽

Cited By ~ 1

Author(s):

Yuji Tohda ◽

Takashi Iwanaga ◽

Hisao Uejima ◽

Yukio Nagasaka ◽

Shigenori Nakajima

Keyword(s):

Lung Cancer ◽

Alveolar Macrophages ◽

Peripheral Blood ◽

Interleukin 2 ◽

Oxygen Radical ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Cancer Group ◽

Radical Production ◽

Oxygen Radical Production

The effects of cytokines (interleukin-2, tumor necrosis factor-alpha and interferon-gamma) on the ability of peripheral blood monocytes and alveolar macrophages to produce oxygen radicals were examined by the chemiluminescence assay in patients with lung cancer. Oxygen radical production by peripheral blood monocytes before stimulation with cytokines was lower in the lung cancer group than in healthy controls, suggesting reduced immune function in lung cancer patients. However, the activity in the lung cancer group was elevated to the control level when the monocytes were stimulated by any of the three aforementioned cytokines. Oxygen radical production by alveolar macrophages did not differ significantly between nonstimulated monocytes from lung cancer patients and those from healthy controls. In the lung cancer group, stimulation of the macrophages with any of the three cytokines elevated their ability to produce oxygen radicals to the same extent as in the control group. The results suggest that stimulation of macrophages by interleukin-2, tumor necrosis factor-alpha or interferon-gamma can exert an antitumor action in patients with lung cancer.

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