Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with lung cancer (LC) have a reduced T-cell proliferative response to phytohemagglutinin (PHA) compared with that of healthy individuals. This decreased response is a result of an inhibitory effect exerted by the monocytes as evidenced by: (1) a restoration to normal levels of the response to PHA when the peripheral blood mononuclear cells were depleted of adherent cells (AD) and (2) a dose-dependent inhibition of the response to PHA when the nonadherent cell population was co-cultured with increasing numbers of autologous AD cells. The addition of indomethacin to the cultures resulted in only a partial restoration of the response to PHA. Monocyte production of interleukin-1 from patients with LC in response to lipopolysaccharide was normal. These findings support the hypothesis that the AD cell population plays a major role in the low T-cell proliferative response to PHA in patients with LC. This suppressor effect is partially mediated by the prostaglandins released by the monocytes.
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PMID:Contribution of monocytes to the decreased lymphoproliferative response to phytohemagglutinin in patients with lung cancer. 187 82

The abilities of human alveolar macrophages (AM) obtained from healthy donors and patients with lung cancer to produce tumor necrosis factor (TNF) were compared with those of their blood monocytes after activation with lipopolysaccharide (LPS). TNF activity was assayed by measuring cytotoxicity against actinomycin D-treated L929 cells and TNF was determined quantitatively by sandwich enzyme-linked immunosorbent assay (ELISA) with polyclonal and monoclonal antibodies against TNF-alpha. Unstimulated AM from healthy donors released variable amounts of TNF spontaneously, whereas blood monocytes did not. When treated with LPS for 24 h, AM and monocytes produced TNF dose-dependently, but TNF production by AM was significantly more than that by blood monocytes. This TNF activity was inhibited completely by monoclonal anti-TNF-alpha antibody. Macrophages generated by in vitro maturation of monocytes induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) produced more TNF than freshly isolated monocytes. No difference was found in the abilities of AM from healthy donors and patients with lung cancer to produce TNF after activation stimuli. These observations suggest that human AM may be important in in vivo antitumor defense of the lung through TNF-alpha production.
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PMID:Production of tumor necrosis factor-alpha by alveolar macrophages of lung cancer patients. 211 92

Leukocytes were obtained from bronchoalveolar lavages (BAL) of 36 patients including 10 with lung cancer, 15 with inflammatory lung diseases and 11 healthy control patients undergoing diagnostic investigation. The entire alveolar cell population responded weakly to the classic interferon (IFN) inducers: Newcastle disease virus (NDV), phytohemagglutinin (PHA) and lipopolysaccharide (LPS). This refers mainly to normal healthy volunteers. Alveolar leukocytes from patients with inflammatory lung diseases and nonsteroid treated lung cancer responded better to the interferon inducers than did cells from other patients. The IFN-alpha or IFN-gamma response of whole blood leukocytes to the same inducers was 10 to 100-fold higher than that of the alveolar cells. Alveolar macrophages from 6 healthy individuals and 3 patients with inflammatory lung disease were cultured in vitro for 6 days. The IFN response to inducers appears to depend on the origin of the cultured cells. It increased in the initially hyporeactive macrophages from healthy subjects and decreased in the relatively reactive cells from the patients with inflammatory lung diseases. We suggest that the hyporeactivity to IFN induction is a physiological state of the alveolar leukocytes which are a specialized cell population having constant exposure to inhaled agents such as dust, smoke, microorganisms and their by-products. The hyporesponsiveness to IFN induction of the alveolar cells may have an important physiological role in protecting lungs against hyperproduction of cytokines involved in the inflammatory and allergic reactions.
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PMID:Hyporesponsiveness of human alveolar leukocytes to interferon-alpha and interferon-gamma inducers. 212 76

The effects of cryopreservation on bacterial lipopolysaccharide (LPS)-induced interleukin-1 (IL-1) production by unfractionated mononuclear cells (MNCs), adherent cells (ACs), and nonadherent cells (NACs) were studied. Culture supernatants from cryopreserved cells contained significantly larger concentrations of IL-1 [MNCs, 211 +/- 50; ACs, 640 +/- 41; NACs, 116 +/- 19 U/ml (mean +/- SEM)] as compared with supernatants from fresh cells (69 +/- 22, 427 +/- 69, and 72 +/- 33 U/ml, respectively). In addition, supernatants obtained from cocultures of autologous fresh and frozen cells contained much less than the expected quantities of IL-1 (78 +/- 8%), indicating that suppressor cells in the fresh population are responsible for the decreased IL-1 content. The studies suggest that functional inactivation of cryosensitive suppressor monocytes is associated with an increase in IL-1 production by the other subset. The results provide further evidence that lack of active suppressor monocytes and increased IL-1 production may be responsible for the previously reported enhanced plaque-forming cell responses of cryopreserved cells from normal controls and from patients with lung cancer.
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PMID:Cryopreservation enhances interleukin-1 production in human mononuclear cells. 213 99

The effects of lung cancer on the abilities of blood monocytes to produce interleukin-1 and to mediate antitumor activity were examined. The functional integrity of blood monocytes was determined by their capacity to respond in vitro to a variety of activating agents and become tumoricidal, as assessed by a radioactive release assay and ability to produce interleukin-1 in vitro. The results show that the presence of lung cancer significantly increased the number of harvested blood monocytes and that the spontaneous tumoricidal activity of these monocytes was slightly high as compared to monocytes obtained from healthy donors. The production of interleukin-1 by monocytes of healthy donors and lung cancer patients was similar. Blood monocytes obtained from lung cancer patients were less cytotoxic against allogeneic A375 melanoma cells as compared with those of healthy donors subsequent to incubation with a soluble muramyl dipeptide analog or lipopolysaccharide, but were as tumoricidal as those from healthy donors when activated with lipophilic muramyl tripeptide (MTP-PE) entrapped in multilamellar liposomes. The finding that monocytes of patients with lung cancer can respond to MTP-PE encapsulated in liposomes, recommends the use of these liposomes in therapy of human lung cancer.
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PMID:Tumor cytotoxicity and interleukin 1 production of blood monocytes of lung cancer patients. 230 25

Interleukin-1 (IL-1) release by alveolar macrophages (AMs) from 29 patients with primary bronchogenic carcinoma, lung metastases, acute pneumonitis, and chronic infection was evaluated in response to a standard stimulus, lipopolysaccharide (LPS). The results were compared to those of AMs from normal smokers or nonsmokers (volunteers). AMs derived from healthy smokers secreted significantly more IL-1 than AMs from nonsmokers. In contrast, AMs from smokers affected with primary lung cancer have lost their capacity of secreting high levels of IL-1, whereas IL-1 secretion was high in nonsmokers with hematogenous metastases. AMs release high IL-1 levels in patients with acute bacterial infections. A significant correlation exists between numbers of AMs and IL-1 levels in normal individuals, a relationship which disappears in patients. These observations suggest that AMs in inflammatory lung disease, even discrete, have an increased capacity to secrete IL-1 on stimulation with LPS. They also suggest that an intrinsic dysfunction of AMs may accompany primary bronchogenic carcinoma. The influence of tobacco in modifying the functions of AMs is stressed.
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PMID:Interleukin-1 secretion by lipopolysaccharide-stimulated alveolar macrophages. Relationships to cell numbers--influence of smoking habits. 281 73

Studies were made to determine whether freshly isolated monocytes from healthy donors could influence the induction of lymphokine (IL-2)-activated killer (LAK) activity. Highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated by counter-flow centrifugal elutriation from peripheral blood. Lymphocytes incubated for 4 days with IL-2 showed significant LAK activity against natural killer (NK) cell-resistant target (Daudi) cells, whereas monocytes treated for 4 days with IL-2 and/or IFN-gamma were not cytotoxic. Under the experimental conditions used, addition of monocytes to the lymphocyte cultures resulted in significant augmentation of the LAK activity, depending on the density of monocytes added. In contrast, monocytes stimulated by lipopolysaccharide (LPS) markedly suppressed LAK activity induced by IL-2, depending on the dose of LPS added. Similar up- and down-regulations of LAK cell induction by monocytes were observed with 4 lines of human lung cancer cells as targets for LAK activity. Although supernatants from untreated monocytes did not increase LAK induction, supernatants from LPS-stimulated monocytes suppressed LAK induction. The regulatory role of monocytes could not be replaced by the addition of exogenous interleukin I (IL-I) or tumor necrosis factor (TNF). Prostaglandin E did not seem to play a regulatory role, since addition of indomethacin did not affect the regulation of LAK cell induction by monocytes. These results clearly indicate that human monocytes may cause up- or down-regulation of the expression of IL-2-induced LAK activity, depending on their functional state.
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PMID:Up- and down-regulation of human lymphokine (IL-2)-activated killer cell induction by monocytes, depending on their functional state. 282 45

Human alveolar macrophages (AMs) and blood monocytes were obtained from 65 smoking and nonsmoking normal volunteers and 29 patients with lung cancer. The oxidative metabolic response of these cells was measured by superoxide anion production after incubation with lipopolysaccharide. In addition, tumoricidal activity of AMs and monocytes was assessed against [3H]thymidine-labeled tumor target cells. Smoking was associated with depressed AM superoxide anion responses in normals but not in patients. In contrast, smoking appeared to slightly elevate monocyte superoxide anion activity. AMs and monocytes exposed to lipopolysaccharide or recombinant gamma-interferon showed tumoricidal activity in all groups. Mean cytotoxicity values of smoking patients versus smoking normals and exsmoking patients versus nonsmoking normals were not significantly different. Smoking, however, in both patients and normals was associated with significantly (P less than 0.005) depressed AM cytotoxicity levels (less than 40%) compared to nonsmoking volunteers and exsmoking patients. Activated AMs from cancer patients and normals were cytotoxic against three different tumorigenic cell lines but not against a nontumorigenic line. No correlation between monocyte and AM cytotoxic activity within single individuals was found. We conclude that AM and monocytes from smoking and exsmoking patients can be activated after exposure to immunomodulators; however, smoking may be slightly suppressive to cytotoxic responses. These studies provide a rationale for clinical trials of immunomodulators in patients with lung cancer.
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PMID:Induction of in vitro tumoricidal activity in alveolar macrophages and monocytes from patients with lung cancer. 283 66

We studied the function of monocyte-mediated suppression in the proliferative responses of depressed T-cells of patients with advanced lung cancer, with both local (Stage III) and extrapulmonary metastasis (Stage IV). The mononuclear cells of 13 non-treated patients showed a significant drop in proliferation upon stimulation with suboptimum, optimum and supraoptimum doses with regards to normal controls (p less than 0.001). On treating T-cells with indomethacin, lymphoblastic transformation increased in both groups (patients and controls), but was significantly greater in the patient group (p less than 0.001). The lipopolysaccharide (LPS) exerted an inhibitory effect on the suppressor cells of normal individuals, yet failed to do so in the case of patients treated either with or without indomethacin. The stimulation of the patients mononuclear cells with PWM failed to increase proliferation, and was not affected by either indomethacin of LPS. Our conclusions are as follows: Patients with lung cancer present a drop in mononuclear cell proliferation when stimulated with PHA; This phenomenon may be due to an exacerbation of the immune systems suppressor function; One of the suppressor mechanisms is prostaglandin-dependent and mediated by monocytes; The B-cells have no relevant functions.
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PMID:Mechanism of suppression of the depressed lymphocyte response in lung cancer patients. 293 Oct 10

Normal human alveolar macrophages (AM) significantly and reproducibly suppress induction of IL 2-activated killer (LAK) cell activity against allogeneic Burkitt's lymphoma (Daudi) cells. Incubation of purified peripheral blood lymphocytes for 4 days with autologous AM and 1 U/ml of IL 2 resulted in AM-mediated suppression of LAK activity, whereas peripheral blood monocytes isolated freshly by centrifugal elutriation from the same donor potentiated induction of LAK activity by IL 2. The suppression of LAK cell induction by human AM was dependent on the density of AM added to the lymphocyte cultures. Recombinant IFN-gamma did not affect AM-mediated suppression of LAK cell induction by IL 2. Both AM and monocytes stimulated with lipopolysaccharide markedly suppressed LAK cell induction by IL 2. AM-mediated down-regulation was seen only when AM were added immediately after the start of incubation of lymphocytes with IL 2; AM potentiated LAK activity when added 1 day later. Similar AM-mediated suppression of LAK cell induction was observed with four lines of allogeneic lung cancer cells as targets for LAK activity. These results indicate that AM may be important in regulation of in situ induction of LAK activity in the lung.
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PMID:Effects of human alveolar macrophages on the induction of lymphokine (IL 2)-activated killer cells. 349 1


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