Prostaglandin E2 production by Mac-2+ macrophages: tumor-induced population shift. 1987

A P Malick, and K D Elgert, and R E Garner, and N F Adkinson
Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg 24061.

Tumor growth induced a shift in the phenotype of macrophages (M luminal diameter) responsible for factor-mediated suppression of allogeneic mixed lymphocyte reactions (MLR), and the suppression by tumor-bearing host (TBH) Mac-2+ M luminal diameter was in part due to production of prostaglandin E2 (PGE2). Thioglycollate-elicited peritoneal M luminal diameter from normal and TBH BALB/c mice were modulated with anti-Mac-1, -2, or -3 monoclonal antibodies (mAb) or depleted with mAb plus complement and cultured in the presence or absence of indomethacin. Culture supernatants derived from mAb plus complement-depleted M luminal diameter were added to the MLR at time of initiation and showed that the suppressor phenotype shifted from Mac-3+ in the normal host to Mac-2+ in the TBH. Mac-1+ M luminal diameter also appeared to be involved in suppression by normal host, but not TBH, M luminal diameter. Loss of MLR suppression (increase in MLR reactivity) correlated with an increase in protein content of the culture supernatants. In an effort to explain both this relationship and the mechanism of MLR suppression, PGE2 levels of culture supernatants were determined by radioimmunoassay. Mac-1+ M luminal diameter were involved in the regulation of PGE2 production in normal hosts, as both activation and depletion caused an increase in PGE2 production. Depletion caused a more dramatic increase in PGE2 production than did activation, suggesting that Mac-1+ M luminal diameter had a dampening effect on PGE2 production. In contrast, no Mac-1+ M luminal diameter-mediated regulatory function occurred in the TBH. Mac-3+ M luminal diameter were involved in the regulation of PGE2 production in both normal and TBH. Mac-2+ M luminal diameter were the primary producers of PGE2 in the TBH, but not in the normal host, as their depletion in the TBH caused a significant loss of PGE2 production. Thus, immunosuppression in the TBH was at least partly due to the inability of Mac-1+ and/or Mac-3+ M luminal diameter to control production of PGE2 by Mac-2+ M luminal diameter.

UI MeSH Term Description Entries
D007213 Indomethacin A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D007959 Lymphocyte Culture Test, Mixed Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens. Leukocyte Culture Test, Mixed,Mixed Lymphocyte Culture Test,Mixed Lymphocyte Reaction,Mixed Leukocyte Culture Test,Mixed Leukocyte Reaction,Leukocyte Reaction, Mixed,Leukocyte Reactions, Mixed,Lymphocyte Reaction, Mixed,Lymphocyte Reactions, Mixed,Mixed Leukocyte Reactions,Mixed Lymphocyte Reactions
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008297 Male Males
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D010529 Peritoneal Cavity The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the STOMACH. The two sacs are connected by the foramen of Winslow, or epiploic foramen. Greater Sac,Lesser Sac,Omental Bursa,Bursa, Omental,Cavity, Peritoneal,Sac, Greater,Sac, Lesser
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D011458 Prostaglandins E (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities. PGE
D005354 Fibrosarcoma A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed) Fibrosarcomas
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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