共查询到20条相似文献,搜索用时 15 毫秒
1.
S Sone N Inamura S M Singh A Okubo H Yanagawa M Nakanishi T Ogura 《Japanese journal of cancer research》1989,80(7):662-669
The susceptibilities of human blood monocytes and alveolar macrophages (AM) to cytotoxicity mediated by lymphokine (IL-2)-activated killer (LAK) cells were examined. Monocytes and AM of healthy donors were obtained by counter-flow centrifugal elutriation (CCE) and bronchoalveolar lavage, respectively. The LAK activity induced by incubation of blood mononuclear cells (MNC) for 4 days with recombinant interleukin 2 (IL-2) was measured by a 4-h 51Cr release assay. The LAK cells were not cytotoxic to freshly isolated monocytes, but were cytotoxic to autologous fresh AM and monocytes that had been incubated for more than 4 days in medium alone. Blood monocytes that had been incubated for 4 days in medium with granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) or interleukin 3(IL-3) were much more susceptible than untreated monocytes to the cytotoxicity of LAK cells. When blood monocytes were separated by CCE into subpopulations of three sizes (small, medium and large), the medium- and large-sized monocytes showed greater responses to GM-CSF in terms of DNA synthesis and colony formation than the small-sized cells. After treatment with GM-CSF for 4 days, these medium and large monocytes were more susceptible than the small monocytes to the cytotoxic action of LAK cells. These results suggest that LAK cells may be important in situ in down-regulating the functions of mature macrophages and blood monocytes that have responded to GM-CSF. 相似文献
2.
S M Singh S Sone N Inamura T Ogura 《International journal of cancer. Journal international du cancer》1989,44(1):170-176
The role of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in monocyte-mediated up-regulation of lymphokine-activated killer (LAK) cell induction by IL-2 was examined. Treatment of blood mononuclear cells (MNC) of healthy donors with GM-CSF for 4 days in the presence of IL-2 resulted in a significant increase in LAK activity against natural killer (NK)-resistant Daudi cells, as assessed by the 4 hr 51Cr-release assay. For determination of the role of GM-CSF in LAK induction, highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated from MNC by counter-flow centrifugal elutriation (CCE). Pre-treatment of monocytes for 4 days with GM-CSF before addition of lymphocytes plus IL-2 resulted in a significant dose-dependent increase in monocyte-mediated up-regulation of LAK induction, but in the absence of monocytes GM-CSF had no effect on LAK cell induction. Similarly, GM-CSF augmented the proliferative response of lymphocytes to IL-2 in the presence of monocytes as assessed by 3H-TdR uptake. Treatment with anti-GM-CSF antibody completely abolished up-regulation of LAK induction by GM-CSF-treated monocytes. When blood monocytes were separated into 5 fractions by CCE, GM-CSF-responding monocytes were found to be responsible for up-regulation of LAK induction. These results suggest that GM-CSF may be important in monocyte-mediated up-regulation of LAK cell induction in vivo. 相似文献
3.
Induction of human monocyte susceptibility to lymphokine-activated killer cell lysis by granulocyte-macrophage colony-stimulating factor 总被引:1,自引:0,他引:1
We have recently reported that cultured human monocytes are susceptible to lysis by autologous lymphokine-activated killer (LAK) cells. In an attempt to modulate the sensitivity of monocytes to LAK-mediated lysis, monocytes were cultured in the presence of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF was found to enhance the susceptibility of monocytes to lysis by LAK cells by 2- to 5-fold over that of untreated cells in a dose-dependent manner. As little as 10 units of GM-CSF per milliliter was sufficient to induce increased sensitivity. In a kinetics study, susceptibility of monocytes increased after 2 days of incubation with GM-CSF, with peak sensitivity occurring from 4 to 6 days of culture. The effect of GM-CSF appeared to be specific for monocytes within the circulating peripheral blood cells because nonadherent cells (NAC) and granulocytes, which are normally resistant to LAK-mediated lysis, did not become susceptible after treatment with GM-CSF. In cold-target inhibition experiments, unlabeled GM-CSF-treated monocytes, but not untreated monocytes, could block the lysis of FMEX, a human melanoma tumor cell line, as well as freshly isolated tumor cells. Finally, LAK cells specifically bound to GM-CSF-treated monocytes in significantly higher percentages than to control monocytes. In summary, our results indicate that GM-CSF was capable of enhancing the susceptibility of monocytes to LAK lysis possibly via increased binding or expression of target structure(s). 相似文献
4.
The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), a pluripotent cytokine, on tumoricidal activity of alveolar macrophages and monocytes from nonsmoking normal volunteers was compared using [3H]thymidine-labeled human tumor cells (SK-MEL-28, melanoma) as targets. A dose-response study (500-5000 units/ml) of recombinant GM-CSF indicated dramatic differences between cytotoxicity of alveolar macrophages and blood monocytes. Macrophages exhibited significant (P less than 0.01) tumoricidal activity at all GM-CSF doses tested. In contrast, monocytes showed no significant tumoricidal activity at 500 units/ml and significantly (P less than 0.01) less activity than alveolar macrophages at doses of 1000-5000 units/ml. Maximal activity in alveolar macrophages occurred 72-96 h after exposure to 1000-5000 units/ml GM-CSF. Tumoricidal activity may be related to the state of maturation, because monocytes matured in vitro for 7 days displayed enhanced tumoricidal activity after GM-CSF exposure. Tumor necrosis factor alpha and interleukin 1 beta were measured in supernatant fluids of 24-h GM-CSF-treated cells. No significant increase in either cytokine was detected after GM-CSF treatment of alveolar macrophages. Monocyte interleukin 1 beta secretion was not enhanced by GM-CSF; however, tumor necrosis factor alpha secretion was enhanced in some donors (three of five). Superoxide anion production of alveolar macrophages was not enhanced by GM-CSF. These data suggest that alveolar macrophage tumoricidal activity is induced by GM-CSF and is not dependent on oxidative metabolism or secreted forms of interleukin 1 beta or tumor necrosis factor alpha. 相似文献
5.
Efficient generation of dendritic cells from alveolar and pleural macrophages as well as blood monocytes in patients with lung cancer. 总被引:2,自引:0,他引:2
Y Suzuki H Yanagawa Y Nishioka N Nishimura E Takeuchi S Sone 《Lung cancer (Amsterdam, Netherlands)》2001,34(2):195-205
In this study, we investigated the generation of dendritic cells (DCs) from blood monocytes and mature macrophages from untreated primary lung cancer patients. Blood monocytes were separated by adherence from blood mononuclear cells (MNC) from ten lung cancer patients and ten control subjects, and cultured for 7 days in medium with granulocyte/macrophage colony-stimulating factor (GM-CSF) plus interleukin (IL-) 4. In all cases examined, DCs with typical characteristics were obtained even in lung cancer patients after 7 days culture with these cytokines, and there was no significant difference in phenotype and stimulatory activity in allogeneic lymphocyte proliferation between DCs derived from monocytes from lung cancer patients and those from control subjects. Next, we examined whether alveolar and pleural macrophages in malignant pleural effusion separated by magnetic beads could differentiate to immunostimulatory DCs. Conventional culture conditions with GM-CSF and IL-4 did not induce efficient numbers of DCs from mature macrophages, whereas the addition of tumor necrosis factor-alpha (TNF-alpha) to GM-CSF and IL-4 effectively contributed to generate DCs. These findings suggest that both mature macrophages and blood monocytes from lung cancer patients could differentiate to DCs, and might be a useful source of DCs for immunotherapy. 相似文献
6.
Up- and down-regulation of human lymphokine (IL-2)-activated killer cell induction by monocytes, depending on their functional state 总被引:8,自引:0,他引:8
A Nii S Sone T Utsugi H Yanagawa T Ogura 《International journal of cancer. Journal international du cancer》1988,41(1):33-40
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. 相似文献
7.
Production of tumor necrosis factor-alpha by alveolar macrophages of lung cancer patients 总被引:2,自引:0,他引:2
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. 相似文献
8.
Production of Tumor Necrosis Factor-α by Alveolar Macrophages of Lung Cancer Patients 总被引:1,自引:1,他引:0
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 immnnosorbent assay (ELISA) with polyclonal and monoclonal antibodies against TNF-α. 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-α 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-α production. 相似文献
9.
Inhibition of lymphokine-activated killer cell function by human alveolar macrophages 总被引:1,自引:0,他引:1
Tissue- and organ-specific factors may be important in the regulation of cytotoxic lymphocytes. We therefore examined the ability of human alveolar macrophages (AMs) to alter the tumoricidal function of lymphokine-activated killer cells (LAK cells). AMs, obtained by bronchoalveolar lavage from healthy volunteers, or peripheral blood monocytes were added to a standard 4-h chromium release LAK assay at varying concentrations. AMs severely inhibited the killing of both NK-sensitive (K562) and NK-resistant (M14) tumor cells [42 +/- 2.6% (SEM) inhibition of M14 killing at the 0.125:1 AM:LAK ratio and 83 +/- 2.3% inhibition at the 1:1 ratio, n = 9]. Peripheral blood monocytes, in contrast, were only one-eighth as inhibitory as AMs. A positive smoking history was associated with a 3- to 7-fold increase in the number of AMs recovered by bronchoalveolar lavage but had no effect on the inhibition produced per AM cell. The mechanism of inhibition was investigated. Formalin fixation produced an 8-fold reduction in the inhibitory capacity of AMs, suggesting the need for active metabolism or an intact cell membrane. No soluble mediator could be detected with a two-chamber Transwell system, in 24-h AM culture supernatants, or following blocking experiments with indomethacin, catalase, or superoxide dismutase. Binding studies demonstrated selective binding between LAK cells and AMs, yet AMs were not susceptible to LAK-mediated lysis under the usual assay conditions. In summary, AMs are potent inhibitors of in vitro LAK function. Inhibition requires direct cell contact and is independent of soluble reactive oxygen species, prostaglandins, or activation by tobacco smoking. Inhibition is not due to lysis of the AM as a competitive cold target. These results suggest that AMs may actively limit antitumor cytotoxic responses in the lung. 相似文献
10.
Impaired tumoricidal function of alveolar macrophages from patients with non-small cell lung cancer. 总被引:1,自引:0,他引:1
The capacity of alveolar macrophages and peripheral blood monocytes from patients with non-small cell lung cancer to develop tumoricidal function after in vitro stimulation with different macrophage activators was investigated. Alveolar macrophages were found to be impaired in their ability to develop cytotoxic activity compared with either the peripheral blood monocytes from the same patients or alveolar macrophages from patients with nonmalignant lung disorders. This result was observed consistently under diverse culture conditions and with different macrophage activators including gamma-interferon (gamma-IFN), granulocyte-macrophage colony-stimulating factor (GM-CSF), phorbol myristate acetate, or endotoxin. The impairment in tumoricidal function observed in alveolar macrophages was not associated with reduced target cell binding compared to peripheral blood monocytes. Alveolar macrophages from patients with lung cancer were found to secrete significantly greater amounts of tumor necrosis factor (TNF) and interleukin-1 (IL-1) than either peripheral blood monocytes from the same patients or alveolar macrophages from the patients with nonmalignant disorders. These results are consistent with either different regulatory pathways for cytotoxicity and cytokine secretion in the alveolar macrophages of patients with lung cancer or diversity in the subpopulations of cells responsible for these functions. 相似文献
11.
M J Thomassen M Ahmad B P Barna J Antal H P Wiedemann D P Meeker J Klein L Bauer V Gibson S Andresen 《Cancer research》1991,51(3):857-862
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes the proliferation and differentiation of hematopoietic progenitor cells. Although preliminary data are available from clinical trials, the effect of GM-CSF on gene expression of immunocompetent cells in treated patients has not been studied. We previously demonstrated that in vitro treatment with GM-CSF also enhances maturation-related anti-tumor activities in mononuclear phagocytes. The purpose of the present study was to examine the effects of in vivo recombinant GM-CSF therapy on alveolar macrophages and blood monocytes, to determine if these cells demonstrated differential expression of cytokine genes, cytokine production, and tumoricidal activity. Alveolar macrophages and blood monocytes were isolated from 13 patients receiving a range of GM-CSF doses (60-250 micrograms/m2/day) by continuous infusion over a 2-week period. Both monocytes and macrophages were isolated prior to therapy and at day 10 of the infusion. Monocytes, in addition, were isolated on day 3 of infusion. Results indicated that GM-CSF therapy enhanced expression of tumor necrosis factor, interleukin 1, and interleukin 6 mRNA in both monocytes and alveolar macrophages. Differential responses, however, were observed in cytokine secretion; monocytes demonstrated enhanced secretion of all three cytokines by day 3 of treatment, but alveolar macrophages showed only enhanced interleukin 6 secretion at day 10. Monocyte tumoricidal activity after in vitro lipopolysaccharide stimulation was also significantly elevated by day 3 of treatment, but at day 10 activity was not statistically different from pretreatment values in either monocytes or alveolar macrophages. These data indicate that GM-CSF exerts striking time-dependent modulatory effects on gene expression and functional activities of monocytes and alveolar macrophages in vivo, although the responses of the two cell types differ with respect to cytokine secretion. 相似文献
12.
Heterogeneity of human lymphokine (IL-2)-activated killer (LAK) precursors and regulation of their LAK induction by blood monocytes 总被引:9,自引:0,他引:9
S Sone N Inamura A Nii T Ogura 《International journal of cancer. Journal international du cancer》1988,42(3):428-434
Highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated by CCE from peripheral blood of healthy donors. Blood lymphocytes were separated by this CCE into 9 subpopulations. The NK activities of these lymphocyte fractions against NK-sensitive K-562 cells and their LAK activities against NK cell-resistant target (Daudi) cells were assayed promptly or after incubation of the fractions for 4 days with or without an optimal concentration of IL-2. NK and LAK activities were measured by 4-hr 51Cr-release assay. On the basis of their NK and LAK activities, these lymphocyte fractions were classified into 3 subpopulations of LAK precursors: one lacking both NK and LAK activities (Fr.2), one with moderate NK activity but low LAK activity (Fr.5), and one possessing both NK and LAK activities (Fr.8). Addition of autologous fresh monocytes to the lymphocyte cultures resulted in a significant increase in induction of LAK activity in Fr.2 and Fr.5. This up-regulation of lymphocytes in Fr. 2 and Fr.5 by monocytes was confirmed in parallel experiments by measuring the blastogenic response of the lymphocytes to IL-2. Deletion of lymphocytes in Fr. 8 of CD16+ (Leu-11+) NK cells resulted in 74% reduction in LAK induction, whereas depletion of mixtures of monocytes and lymphocytes in Fr. 2 of cells reacting with CD3+ (OKT3+) antibody resulted in a 66% reduction in LAK induction. This up-regulation of LAK cell induction from LAK precursors by monocytes was confirmed using 4 lines of human lung cancer cells as targets for LAK activity. These results clearly indicate that human monocytes may cause up-regulation of the expression of IL-2-induced LAK activity in T cells and in a subpopulation of NK cells. 相似文献
13.
Susceptibility to lysis of pulmonary alveolar macrophages by human lymphokine-activated killer cells
R Zambello L Trentin C Feruglio P Bulian M Masciarelli A Cipriani C Agostini G Semenzato 《Cancer research》1990,50(6):1768-1773
In this study we addressed the question of whether lymphokine-activated killer (LAK) cells, besides killing neoplastic cells, may exert a certain degree of lysis on the normal counterpart; in particular we took into consideration the toxicity against pulmonary alveolar macrophages (PAM). We demonstrated that human LAK cells generated in vitro following incubation of peripheral blood mononuclear cells with recombinant interleukin 2 for 4 days were able to lyse normal PAM in a 4-h 51Cr release assay. Similarly, PAM recovered from patients suffering from nonneoplastic interstitial lung disorders, i.e., sarcoidosis and hypersensitivity pneumonitis, were shown to be susceptible to the cytotoxic function provided by LAK cells. Both autologous and allogeneic PAM were lysed by LAK cells, thus suggesting that the phenomenon we observed does not require a major histocompatibility complex restriction. Preincubation of PAM under study with gamma-interferon did not affect their susceptibility to the lysis mediated by LAK cells. Furthermore, cold target inhibition assay demonstrated that normal PAM could efficiently compete with both NK-sensitive and NK-resistant target lines for the binding sites on LAK cells, thus indicating that the putative receptor(s), or at least the mechanism of target recognition, is shared by PAM and these different target cell lines. The evidence herein provided that LAK cells are cytotoxic to normal, nontransformed PAM points out that the pathogenetic mechanisms involving this self-addressed lytic activity could account for some adverse reactions related to LAK/interleukin 2 immunotherapy. 相似文献
14.
Keiji Takahashi Saburo Sone Seiya Saito Yoshitaka Kamamura Tadashi Uyama Takeshi Ogura Yasumasa Monden 《Cancer science》1995,86(9):861-866
The role of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in augmentation of lymphokine-activated killer (LAK) cell induction by interleukin-2 (IL-2) from pleural cavity mononuclear cells (PCMNCs) was examined in sixteen patients with resectable primary lung cancer not associated with malignant effusion. None of the patients had received any anticancer therapy prior to this study. Incubation of PCMNCs of patients without malignant effusion with GM-CSF for 4 days in the presence of IL-2 resulted in a significant increase in LAK activity against natural killer-resistant Daudi cells. This result was obtained by using the 4 h 51 Cr-release assay. PCMNCs and blood mononuclear cells (BMNCs) were harvested simultaneously from pleural cavity lavage fluid and peripheral blood in lung cancer patients. The LAK activity developed from PCMNCs and BMNCs following incubation with IL-2 for 4 days, but the LAK activity from PCMNCs was significantly lower than that from BMNCs ( P < 0.05). Incubation of PCMNCs with GM-CSF augmented the LAK activity from PCMNCs to a level as high as that from BMNCs. These results suggest that the combined use of GM-CSF with IL-2 may result in augmentation of LAK activity developed from PCMNCs of lung cancer patients without malignant effusion. 相似文献
15.
Lymphokine-activated killer induction and its regulation by macrophages in malignant pleural effusions 总被引:2,自引:0,他引:2
H Yanagawa S Sone A Nii K Fukuta M Nakanishi K Maeda M Honda T Ogura 《Japanese journal of cancer research》1989,80(12):1220-1227
Mononuclear cells (MNC) from pleural effusions and peripheral blood of 18 patients with primary lung cancer with malignant pleural effusion were studied. Pleural and blood MNC generated lymphokine-activated killer (LAK) activity similarly when cultured for 4 days with an optimal concentration of interleukin 2 (IL-2). Highly purified lymphocytes (greater than 98%) and monocyte-macrophages (greater than 90%) were isolated by discontinuous Percoll gradient centrifugation from pleural and blood MNC. Pleural macrophages, as well as blood monocytes, showed significant augmenting effects on in vitro LAK cell induction from pleural and blood lymphocytes by IL-2. During daily intrapleural administration of IL-2, significant induction of LAK activity in vivo was observed after 3 days, but then this LAK activity in pleural MNC decreased almost to zero by day 15. Daily injections of IL-2 resulted in reduction in the up-regulation of LAK induction by pleural macrophages and also in increases in the levels of soluble IL-2 receptors in pleural effusions. These findings indicate that in vivo LAK induction of lymphocytes in malignant effusions by IL-2 may be regulated by macrophages in the effusions. 相似文献
16.
Hiroaki Yanagawa Saburo Sone Akihiko Nii Katsuyuki Fukuta Mie Nakanishi Ken-ichi Maeda Mitsuo Honda Takeshi Ogura 《Cancer science》1989,80(12):1220-1227
Mononuclear cells (MNC) from pleural effusions and peripheral blood of 18 patients with primary lung cancer with malignant pleural effusion were studied. Pleural and blood MNC generated lymphokine-activated killer (LAK) activity similarly when cultured for 4 days with an optimal concentration of interleukin 2 (IL-2). Highly purified lymphocytes (>98%) and monocyte-macrophages (>90%) were isolated by discontinuous Percoll gradient centrifugation from pleural and blood MNC. Pleural macrophages, as well as blood monocytes, showed significant augmenting effects on in vitro LAK cell induction from pleural and blood lymphocytes by IL-2. During daily intrapleural administration of IL-2, significant induction of LAK activity in vivo was observed after 3 days, but then this LAK activity in pleural MNC decreased almost to zero by day 15. Daily injections of IL-2 resulted in reduction in the up-regulation of LAK induction by pleural macrophages and also in increase in the levels of soluble IL-2 receptors in pleural effusions. These findings indicate that in vivo LAK induction of lymphocytes in malignant effusions by IL-2 may be regulated by macrophages in the effusions. 相似文献
17.
This study examined the lymphokine-activated killer (LAK) cell cytotoxicity on monoclonal antibody (MoAb)-bound tumor cells from the human small cell lung carcinoma cell lines H69 and H128. LAK cells were generated from normal peripheral blood mononuclear cells by incubation with interleukin 2 for 3 or more days. Cells from the LAK culture were cytotoxic to natural killer-sensitive (K562, 84% cytotoxicity) and natural killer-resistant (Daudi, 85%; H69 and H128, 69% and 97%, respectively) cell lines, and to freshly excised human lung (49%) and breast (57%) tumors. LAK cytotoxicity to H69 or H128 cells was significantly augmented by target cell preincubation with the small cell lung carcinoma-reactive MoAbs 1096 (increases of up to 271%) or 5023 (up to 223%). SCLC 5023 or 1096 did not enhance LAK cytotoxicity to Daudi cells of lymphoblastoid origin. Pretreatment of LAK cells with an anti-Fc receptor antibody blocked MoAb augmentation by 1096 or 5023 (but not LAK cytotoxicity), suggesting that LAK-MoAb interaction may be mediated by Fc binding. LAK activity coincided with emergence of a large cell [interleukin 2-stimulated large mononuclear leukocyte (LML)] subset expressing the CD16 and NKH-1 surface determinants. Serial immunophenotyping of the LAK cell culture harvested at Days 3, 5, and 7 indicated that the level of LAK cytotoxicity, with or without MoAb augmentation, correlated with frequency of NKH-1-reactive LMLs. These observations support the hypothesis that LAK cytotoxicity is mediated by a NKH-1-reactive LML subpopulation. Antitumor cytotoxicity may be augmented by tumor-reactive MoAbs through Fc binding to this LML subset. 相似文献
18.
Human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy donors were examined for ability to cause lectin-dependent tumor cell killing. Of five plant and two animal lectins tested, only one lectin, wheat germ agglutinin (WGA), induced significant and reproducible lectin-dependent macrophage-mediated cytotoxicity (LDMC) against human bladder cancer (T-24) cells. There was no significant difference between the LDMCs of AM and blood monocytes. All 6 tumor cell lines tested were sensitive to various extents to LDMC induced by WGA. Quantitative analysis with WGA-FITC conjugate showed the presence of various levels of receptors for WGA on the surface of AM, monocytes and tumors. A relatively good correlation was found between the sensitivities of the tumor cells to LDMC mediated by AM and the numbers of receptors for WGA. Pretreatment of AM or monocytes with LPS did not affect their LDMC. These results indicate that a plant lectin, WGA which binds to both human AM and tumor cells, renders human AM cytotoxic to allogeneic tumor cells by a different mechanism(s) from that involved in the nonspecific tumor cytotoxicity of activated macrophages. 相似文献
19.
Interleukin-12 (IL-12), also known as natural killer cell stimulatory factor (NKSF), was found to induce cytotoxic activity from human blood T cells and NK cells. The present study was undertaken to examine the effect of human alveolar macrophages (AM) on induction by IL-12 cytotoxic cells from blood lymphocytes. AM were obtained by bronchoalveolar lavage from healthy donors. Highly purified lymphocytes (>99%) and monocytes (>90%) were also isolated by centrifugal elutriation from peripheral blood of the same donors. Cytotoxicity of lymphocytes was measured by 4-h 51 Cr release assay. IL-12 stimulated blood lymphocytes to produce interferon γ (IFNγ) and tumor necrosis factor α (TNFα), and this effect was augmented by co-cultivation with monocytes or AM. AM-upregulated induction of cytotoxic lymphocytes was stimulated with IL-12, and this effect was significantly abrogated by addition of antibodies against IFNγ and TNFα. Induction by IL-12 of IFNγ production and cytotoxic activity of CD8+ cells was also augmented by co-cultivation with monocytes or AM. AM were more effective than monocytes in augmenting the cytotoxic activity of IL-12-stimulated lymphocytes and CD8+ cells. These observations suggest that in situ induction of IL-12-stimulated cytotoxic cells in the lung may be regulated by complex cytokine networks, depending on participation of monocytes and alveolar macrophages. 相似文献
20.
K. Pryor J. Goddard D. Goldstein P. Stricker P. Russell D. Golovsky R. Penny 《British journal of cancer》1995,71(4):801-807
A cytotoxicity assay was used to study the action of bacillus Calmette-Guerin (BCG) and cytokines on four human bladder cancer cell lines. Monocytes and lymphocytes from peripheral blood were incubated with or without BCG or cytokines for 24 h, after which [3H]thymidine-labelled target cells were added and the 72 h percentage specific release determined. BCG had a direct cytotoxic effect against tumour cells and significantly enhanced monocyte/macrophage and enhanced lymphocyte cytotoxicity against one cell line (UCRU-BL-17). Supernatants (SNs) from BCG-activated monocytes/macrophages and lymphocytes increased the percentage specific release of [3H]thymidine from UCRU-BL-17 cells. Interferon alpha (IFN-alpha) and interleukin 2 (IL-2) were cytotoxic towards UCRU-BL-17. No synergy occurred between BCG and cytokines at the concentrations tested. The results suggest that BCG is superior to IFN-alpha, interferon gamma (IFN-gamma) and IL-2 in enhancing cell-mediated cytotoxicity. 相似文献