Age-dependent alterations in the tumoricidal functions of tumor-associated macrophages.
Age-dependent tumor cytolytic functions of tumor-associated macrophages (TAM) obtained from mice bearing different stages of Dalton's lymphoma (DL), a spontaneous T cell lymphoma, were studied. Mice were separated into three groups on the basis of their reproductive status as indicator of age: young (prereproductive); adult (reproductive) and old (postreproductive). DL was injected (1 x 10(5) cells/mouse) intraperitoneally in mice; days 4, 10 and 16 from the day of injection were referred to as early, mid and late tumor stages, respectively. Normal peritoneal macrophages and macrophages isolated from the ascitic fluid of DL-bearing mice (TAM); 1 x 10(5) cells activated with lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) and assayed for age-dependent alterations in macrophage tumoricidal functions such as: tumor cell binding, cytotoxicity, production of reactive nitrogen intermediates (RNI), expression of inducible nitric oxide synthase (iNOS) and oncostatin-M (OSM) were observed. TAM from old mice were observed to be inhibited with respect to tumor cell binding, cytotoxicity and expression of iNOS and OSM, as compared to macrophages of young and adult mice. TAM obtained from early tumor stages showed augmented tumor cytotoxicity as well as enhanced expression of iNOS and OSM in all the age groups. This effect was most pronounced in the TAM obtained from adult mice and least in the TAM obtained from old mice. The reasons for the observed difference are discussed. These observations should be helpful in understanding the effect of progressive tumor growth and age on the functions of TAM and their responsiveness towards therapeutic manipulations.
Khare
V
V
School of Biotechnology, Banaras Hindu University, Varanasi, India.
Sodhi
A
A
Singh
S M
SM
D000375:Aging / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism
D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D053683:Oncostatin M; D009569:Nitric Oxide; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D002118:Calcium