Role of alveolar macrophages in tumor-bearing rats: tumoricidal properties of carrageenan-activated macrophages

Tumor BN472, a malignant mammary adenocarcinoma, was subcutaneously transplanted into syngeneic female Brown Norway rats. Seven days after tumor inoculation, carrageenan-impregnated synthetic sponges were subcutaneously implanted in control and tumor-bearing rats. Another week later the animals were sacrificed and alveolar macrophages were harvested and tested for tumoricidal activity against a tissue culture line of BN472 cells and their capacity to phagocytose formaldehyde-treated sheep erythrocytes. The data demonstrate that carrageenan statistically significantly enhances the tumoricidal activity of alveolar macrophages in tumor-bearing rats. Phagocytic activity of the macrophages in these animals is not different from sham-operated control animals, whereas the phagocytic activity of tumor-bearing rats is statistically significantly decreased.     

Induction of in vitro tumoricidal activity in alveolar macrophages and monocytes from patients with lung cancer

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.     

Impaired tumoricidal function of alveolar macrophages from patients with non-small cell lung cancer.

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.     

Possible participation of tumoricidal macrophages in the therapeutic effect of bleomycin on a transplantable rat fibrosarcoma

When bleomycin (BLM) (5 mg/kg/day) was administered i.p. to WKA rats for 5 days from the eighth day after KMT-17 implantation, the therapeutic effects of BLM were demonstrated by complete tumor regression in 50% of the cases and prolongation of the mean survival time of the remainder [survival days, 44.3 +/- 13.6 (SD)]. The combined administration of an antimacrophage agent, carrageenan, with BLM significantly inhibited the therapeutic effects of BLM (cure rate, 33%; survival days, 29.8 +/- 5.8). By means of a Winn assay, the tumor neutralizing activity of both spleen cells and peritoneal cells (PC) against KMT-17 cells was found to be augmented in BLM-treated tumor bearing rats as compared with that in nontreated tumor bearing rats. The enhanced tumor neutralizing activity of spleen cells was not abolished by an anti-rat T-cell serum plus complement treatment and was present in an adherent macrophage enriched population. Similarly, an in vitro [125I]iododeoxyuridine release test enabled us to observe the enhancement of the cytotoxic activity of adherent spleen cells and adherent PC in BLM-treated rats. The cytotoxic activity of the PC of BLM-treated rats was not specific to KMT-17 cells alone but was also observed to operate against antigenically different tumor cells such as WFT-2N, KST-20, and K562 cells. An in vitro carrageenan treatment of PC taken from BLM-treated rats reduced their cytotoxic activity. At the same time, the combined administration of carrageenan and BLM also reduced the cytotoxic activity of PC. These results suggest that the tumoricidal activity of macrophages in tumor bearing rats is augmented after BLM therapy and that the activated tumoricidal macrophages may participate in the host-mediated antitumor effects of BLM.     

Down-regulation by interleukin 4 of activation of human alveolar macrophages to the tumoricidal state

The effect of recombinant human interleukin 4 (IL-4) on the expression of antitumor activity of human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy donors was examined. AM were incubated for 16 h in medium with various macrophage activators [lipopolysaccharide, des-methyl muramyldipeptide, Nocardia rubra cell wall skeleton, and heptanoyl-gamma-D-Glu-(L)-meso-alpha,epsilon-A2pm(L)-D-Al aOH] in the presence or absence of IL-4, and then their tumoricidal activity was assayed by measuring 125I-UdR release from human melanoma (A375) cells. The spontaneous tumoricidal activity of AM was slightly suppressed by IL-4 in 3 of 7 donors. Addition of IL-4 to cultures of AM with the activators resulted in dose-dependent suppression of AM-mediated cytotoxicity against A375 cells. IL-4 also inhibited AM-mediated cytotoxicity against A375-R cells, which are resistant to interleukin 1 (IL-1) and tumor necrosis factor alpha, HT-29 colon cancer cells, and KB cells. IL-4 inhibited the early induction phase of AM activation. Pretreatment of AM with IL-4 also suppressed their expression of antitumor activity in response to lipopolysaccharide. IL-4 inhibited the production of monokines (IL-1 and tumor necrosis factor alpha) by AM at the protein and mRNA levels. These findings suggest that IL-4 may be important in vivo in the down-regulation of antitumor expression of AM in the lung by inhibiting the production of monokines and other killing mechanisms.     

In vitro activation of rat liver macrophages to tumoricidal activity by free or liposome-encapsulated muramyl dipeptide

We investigated the in vitro activation of rat liver macrophages to a tumoricidal state with free and liposome-encapsulated immunomodulators. The cytolytic activity of liver macrophages was determined by a radioactivity release assay using murine B16 melanoma cells, labeled with [methyl-3H]thymidine. Exposure of the liver macrophages to concentrations of 50 micrograms of free, nonencapsulated, muramyl dipeptide (MDP) per ml resulted in maximal levels of tumor cell lysis of approximately 20%. Encapsulation of the MDP within liposomes (multilamellar vesicles, 0.3 to 0.5 micron in diameter, consisting of egg phosphatidylcholine, cholesterol, and dicetylphosphate, 4:5:1) not only caused a 500-fold reduction in the amount of MDP required to obtain the same levels of cytolysis but also increased the maximally obtainable level of cytolysis more than 2-fold. A synergistic effect of lipopolysaccharide and free or encapsulated MDP on cytolytic activity was observed when the macrophages were exposed to a combination of the two agents simultaneously. Besides causing tumor cell lysis, activated macrophages were also able to suppress tumor cell proliferation by 80 to 90% as determined by a [methyl-3H]thymidine incorporation assay. With a fixed amount of MDP, encapsulated in different amounts of liposomal lipid, the extent of macrophage activation was found to increase with a larger amount of encapsulating lipid. This increase in macrophage activation may be the result of a sustained intracellular release of encapsulated MDP from the liposomes. Liposome structure and composition will thus be important parameters in the in vivo application of liposomes as carriers of immunoactive substances.     

Augmentation of tumoricidal activity of human monocytes and macrophages by lymphokines

Monocytes were separated from peripheral blood mononuclear cells of normal human donors by adherence on plastic conditioned by cell lines (microexudate-coated plastic) and harvested by exposure to ethylene diamine tetra-acetic acid. Cytolytic activity was tested by incubating effector cells for 48 h with the murine SV40-transformed TU5 kidney line or the human lung cancer-derived CaLu line prelabelled with tritiated thymidine. Lymphokine-containing supernatants were obtained from in vitrocultures of lymphoid cells with phytohemagglutinin (PHA), purified protein derivative (PPD), or with Corynebacterium parvum strains CN6134 or CNS888. The monocytes had significant levels of spontaneous cytotoxicity and exposure to lymphokine supernatants markedly enhanced their tumoricidal activity. Augmentation of monocyte-mediated cytotoxicity required a minimal exposure to lymphokine supernatants for 4 h and was maximal after 24 h of preincubation. Treatment of the effector cells with anti-human T-cell serum and complement did not affect either their spontaneous or their lymphokine-stimulated cytotoxicity, whereas silica impaired both reactivities. Supernatants of cultures with PHA, PPD and C. parvum CN6134 had significant levels of interferon (IF). Since partially purified human fibroblast or leukocyte IF was able to stimulate monocyte-mediated cytotoxicity, the IF in these supernatants could play some role in the stimulation of the monocytes. However, C. parvum CN5888 supernatants, which had little IF, enhanced monocyte cytotoxicity as effectively as the C. parvum CN6134 supernatants, strongly suggesting that lymphocyte mediators other than IF can augment the tumoricidal activity of these effector cells. Mature macrophages obtained by in vitro cultivation of monocytes for 4-7 days retained natural cytolytic activity and showed enhanced cytotoxicity in the presence of lymphokines. However, more prolonged in vitro cultivation (> 10 days) resulted in cultures of epithelioid and multinucleated cells which had little natural cytotoxicity and were not responsive to lymphokines.     

Herpes simplex virus-induced suppression of macrophage-mediated tumoricidal activity in murine macrophages

Herpes simplex virus (HSV) infections can enhance the progression of neoplastic diseases. Since macrophages can be activated to become tumorilytic and may figure prominently in host defense against cancer, the ability of HSV to modify macrophage-mediated tumoricidal functions was evaluated. Murine peritoneal macrophages treated with HSV could not be activated to a tumoricidal state by mouse recombinant gamma-interferon (IFN-gamma). Addition of HSV 4 h after treatment with IFN-gamma, at a time when the macrophages are fully committed to developing the cytotoxic phenotype, blocked macrophage-mediated lysis of syngeneic melanoma target cells. This inhibition of activation and cytotoxicity was not due simply to uptake of virus particles, because treatment with heat-inactivated HSV at 4-h posttreatment with IFN-gamma had no effect. In addition, HSV did not undergo a productive infection within macrophages, suggesting that the observed inhibitory activity might be due to a virus-induced product. In this regard, treatment of macrophages with recombinant alpha-interferon suppressed the activation of these cells by IFN-gamma, suggesting that virus-induced alpha-interferon may be mediating all or part of the suppressive activity. These studies suggest that enhancement of tumor progression following HSV infection may be related to the virus-induced suppression of macrophage-mediated tumoricidal activity.     

Induction of tumoricidal activity in isolated rat liver macrophages by liposomes containing recombinant rat gamma-interferon supplemented with lipopolysaccharide or muramyldipeptide

We examined whether the macrophages in the liver, Kupffer cells, could be activated to a tumoricidal state in a similar way as has been described for other macrophage types. Kupffer cells were isolated by centrifugal elutriation of pronase-treated rat livers. Incubation with highly purified recombinant rat gamma-interferon in combination with small amounts of lipopolysaccharide or muramyldipeptide resulted in highly cytotoxic macrophages, as measured against P815 tumor cells in an 18 h 51Cr-release assay. Incubation of Kupffer cells with the stimulators entrapped within liposomes, caused phagocytosis of the liposomes and subsequent activation to tumor cytotoxicity, provided that both rat gamma-interferon and subthreshold doses of either lipopolysaccharide or muramyldipeptide were encapsulated. The minimum amount of liposomal rat gamma-interferon that induced optimal activation was 0.5 U/ml, while 6 ng/ml of liposomal lipopolysaccharide or muramyldipeptide was required. Cytotoxicity of Kupffer cells activated in this way, persisted for at least 48 h. Since liposomes in circulation are readily cleared by the liver macrophages, these findings may have therapeutic implications.     

Cytotoxic activity of human pulmonary alveolar macrophages

The functions of human pulmonary alveolar macrophages (PAMs) have been relatively little studied compared with those of their circulating counterparts, blood monocytes. This study examined the ability of human PAMs to kill primary human tumor cell cultures and control normal fibroblasts in vitro. PAMs were derived by bronchial lavage from patients with lung cancer of various histological types and stages, patients with acute or chronic noncancerous pulmonary disorders, and subjects with a presumed illness who proved to be normal. After extensive washing, the PAMs were cocultured with [3H]proline-labeled tumor cells, principally lung cancers and melanomas, at various effector:target ratios for 60 hr. Cytotoxicity was measured by comparing radioactivity associated with the remaining adherent tumor cells cultured in the presence or absence of PAMs. Twenty-eight of 42 preparations of PAMs from 42 individuals were cytotoxic to one or more short-term primary tumor cultures. All 28 specimens from patients with lung cancer or chronic pulmonary disease were cytotoxic; all of the 14 PAM preparations lacking cytotoxicity were from individuals with acute pulmonary disorders or who were proved free of pulmonary disease. PAMs were cytotoxic even at effector:target ratios of 2.5:1 or 1.25:1. Fibroblasts were unaffected at any ratio. Sarcoidosis patients in remission had noncytotoxic PAMs, whereas the disease in relapse was characterized by cytotoxic PAMs. Serial study of 2 patients confirmed a loss of reactivity during remission. Smoking did not correlate with the presence or absence of spontaneous cytotoxicity and did not influence the degree of cytotoxicity in "reactors." Partially purified alpha-interferon enhanced the killing of cytotoxic PAMs in 10 of 21 instances but did not induce cytotoxicity in 9 tests on nonreactive PAMs. We conclude that human PAMs from patients with lung cancer or chronic pulmonary diseases, including active sarcoidosis, were cytotoxic to several recently explanted tumor cell cultures. PAMs from acute pulmonary dysfunctions and those from patients with inactive sarcoidosis were not spontaneously cytotoxic.     

Enhancing effect of human monocytic colony-stimulating factor on monocyte tumoricidal activity

Human monocytic colony-stimulating factor (hM-CSF) enhances several effector functions of human peripheral blood monocytes. In this study, we investigated the effect of the Mr 85,000 form of hM-CSF on the tumoricidal activity of human monocytes against several leukemic cell lines using a 12-h chromium release assay. Human peripheral blood monocytes preincubated with hM-CSF for 48 h showed more effective killing activity towards K562, U937, Daudi, and HL60 cells as compared with the cells preincubated with medium alone. Maximal enhancement of the tumoricidal activity was achieved by hM-CSF at concentrations of 50-100 ng/ml. A trace amount of lipopolysaccharide contained in the hM-CSF did not seem to contribute to the enhancing effect, as the addition of a lipopolysaccharide-neutralizing agent, polymyxin B, to the preincubation mixture did not reduce this effect. Anti-tumor necrosis factor antiserum partially blocked the tumoricidal activity mediated by hM-CSF, indicating that tumor necrosis factor may participate in the hM-CSF-mediated increase of monocyte tumor cell-killing activity. These results suggest that in addition to other monocyte-activating factors, hM-CSF augments monocyte tumoricidal activity against a wide spectrum of tumor targets.     

The effect of anti-CD28 on the CD3-AK proliferation and tumoricidal activity

Objective

The aim of this study was to costimulate the CD3-AK cells with anti-CD28 monoclonal antibody (mAb), observe the effect of cell proliferation and cytotoxicity and explore the regulatory role of CD28 mAb on the CD3-AK tumoricidal activity.

Methods

To prepare CD3-AK cells, observe the number and morphology of the activated T cells with the inverted microscope and detect the inhibitory rate of the myeloma cells by methylthiazolyldiphenyl-tetrazolium bromide (MTT).

Results

Adding the anti-CD28 mAb to the CD3-AK cells, the number of cells increased significantly (P < 0.05) and the cytotoxic activity of the cells was significantly higher (P < 0.05).

Conclusion

The addition of anti-CD28 mAb has a strong synergistic effect, which can effectively enhance the tumoricidal activity of CD3-AK.     

Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes.

Cell-free culture supernatants rich in macrophage-activating factor (MAF) activity obtained from mitogen-stimulated F344 rat lymphocytes have been encapsulated within liposomes of differing size and lipid composition and their ability to render normal mouse macrophages cytotoxic for tumor cells in vitro has been compared with that of unencapsulated (free) MAF added to the extracellular medium. Normal macrophages from C57BL/6, C3H/Hen, and C57BL/6 X C3H F1 mice treated with liposome-encapsulated MAF exhibited significant in vitro cytotoxicity against syngeneic and allogeneic tumor cells but did not kill nontumorigenic normal cells. Dose-response measurements revealed that liposome-encapsulated MAF was able to render macrophages tumoricidal at concentrations of at least 20,000 times lower than free MAF. Liposomes containing MAF were able to activate macrophages in the presence of p-nitrophenyl-2-O-alpha-L-fucopyranosyl-beta-D-galactopyranoside, a potent inhibitor of free MAF, indicating that encapsulated MAF was protected within liposomes and that liposome-mediated activation was not caused by small amounts of MAF released into the culture medium from "leaky" liposomes. Liposome-encapsulated MAF was also able to activate macrophages which were refractory to activation by free MAF following either removal of presumably surface receptors for MAF by pronase and/or alpha-L-fucosidase or occupation of the MAF receptor on macrophages by fucose-binding plant lectins (Ulex europaeus 1 and Lotus tetragonolobus agglutinins). Also, populations of nontumoricidal inflammatory tissue macrophages, which were inherently unresponsive to free MAF, would be rendered tumoricidal in vitro by incubation with liposome-encapsulated MAF. Collectively, the data suggest that MAF can render macrophages tumoricidal by acting on intracellular sites.     

Role of antitumor activity of alveolar macrophages in lung cancer patients

The purpose of this study is to clarify the significance of antitumor activity of alveolar macrophages (AM) in lung cancer patients. AM from tumor-bearing and non-tumor-bearing segments were obtained separately by the lavage of bronchoalveolar tracts of resected lungs of 74 patients with primary lung cancer. Cytostatic activity (CTS) of AM obtained from non-tumor-bearing segments was stable in spite of enlargement of tumor size or progression of N factor. In contrast, CTS of AM obtained from tumor-bearing segments may be augmented at Stage II as compared with Stage I, and suppressed with an advance of stage from II through IV, although the number of Stage II patients was as small as three. Moreover, CTS of AM from tumor-bearing segments was suppressed in N2 as compared with N0 or N1, and also it was suppressed as compared with that of AM from non-tumor-bearing segments in N2 disease. CTS of AM from smokers was suppressed as compared with that of nonsmokers in both tumor-bearing and non-tumor-bearing segments. These results suggest that lung cancer cells or their products may suppress antitumor activity of AM in the tumor-bearing segments at advanced stages, and cigarette smoking is a suppressive factor on antitumor activity of AM.     

Synergistic activation of rat alveolar macrophages by cepharanthine and OK-432

We studied the synergistic activation of rat alveolar macrophages (AM) by cepharanthine (Ceph.) and OK-432. Rat AM could be rendered much more tumoricidal against Walker-256 tumors in vitro after the i.v. injection of ceph. (5 mg/Kg) and OK-432 (5 KE/rat) thao of ceph. or OK-432 only. Radioactivity of 14C-acetate-OK-432 trapped in murine lung after the i.v. injection of mixed of ceph. was much higher than of 14C-acetate-OK-432 only. Rat AM could be rendered tumoricidal by incubation in vitro with OK-432, but not with ceph. This finding suggests that if OK-432 is injected intravenously with mixed of with ceph., of OK-432 is trapped much more up by the lung without mixture, therefore AM can be much more tumoricidal. Intravenous administration of OK-432 with ceph. may be useful for reduction of lung metastasis by tumoricidal AM.     

Similarities among factors that render macrophages tumoricidal in lymphokine and interferon preparations.

Lymphokine preparations, including supernatants derived from antigen-stimulated Bacillus Calmette-Guérin-immune spleen cell cultures and normal spleen cells incubated with insoluble concanavalin A, were compared with partially purified L-cell interferon for the ability to render resting macrophages nonspecifically tumoricidal in vitro. Significant activation of macrophages by lymphokine preparations occurred at concentrations as low as 0.5 and 0.25% of the assay mixture for antigen-stimulated and concanavalin A-induced lymphokine, respectively. These end point concentrations were each determined to contain 0.3 unit of interferon per ml. Supernatants obtained from unstimulated normal spleen cells, concanavalin A-treated nu/nu spleen cells, or Bacillus Calmette-Guérin-immune spleen cells in the absence of sensitizing antigen did not enhance macrophage tumoricidal function and lacked interferon. Activation by L-cell interferon required at least 1 unit/ml. The macrophage-activating factors contained in lymphokine and interferon preparations were stable at pH 2 and at 56 degrees, but they were destroyed when heated at 80 degrees for 30 min, and were inactivated by trypsin. The data demonstrate common properties for the induction of tumoricidal macrophages by these divese preparations.     

Nonselective destruction of murine neoplastic cells by syngeneic tumoricidal macrophages

The purpose of these studies was to select in vitro tumor cells that were resistant to macrophage-mediated lysis. Seven different heterogeneous murine neoplasms (four fibrosarcomas, a melanoma, a rhabdomyosarcoma, and an osteogenic sarcoma) and one cloned line of a fibrosarcoma were incubated in vitro with syngeneic tumoricidal macrophages. Surviving tumor cells were recovered and expanded to undergo subsequent interaction with tumoricidal macrophages. After six sequential interactions, all cell lines were examined for their susceptibility to lysis mediated by murine peritoneal exudate macrophages activated with liposomes containing muramyl tripeptide phosphatidylethanolamine. In all eight systems, no significant differences were detected between the parent tumor cells and cells that survived the sequential interactions. Neither macrophage infiltration into s.c. tumors nor the experimental or spontaneous metastatic potentials of the parental tumors differed from the lines established by cells surviving macrophage-mediated lysis. Collectively, the data suggest that tumor cell destruction by activated macrophages is nonselective and does not lead to the development of resistant tumor cells nor to cells with altered metastatic properties.     

Differential effect of recombinant granulocyte macrophage colony-stimulating factor on human monocytes and alveolar macrophages

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.     

激活小鼠大网膜乳斑及腹腔巨噬细胞杀伤胃癌SGC-7901的研究

目的 观察小鼠腹腔注射干扰素-γ(IFN-γ)、高聚生和新城疫病毒(NDV-L)对激活网膜乳斑及腹腔巨噬细胞杀伤胃癌细胞的作用。方法 用活性炭染色、计算机辅助分析、非特异性脂酶染色、台盼蓝染色计数、扫描电镜及荧光定量PCR方法,观察大网膜乳斑及腹腔巨噬细胞的激活。用MTT法测定巨噬细胞培养上清对人胃癌细胞株SGC-7901的杀伤活性。结果 大网膜乳斑量增多,乳斑巨噬细胞数增多。腹腔巨噬细胞数增多,形态呈激活态,TNF-α和iNOS mRNA表达增多。激活的巨噬细胞对SGC-7901杀伤作用增强。结论 腹腔注射IFN-γ、高聚生和NDV-L,均能激活乳斑及腹腔巨噬细胞,其中以IFN-γ的激活作用最强。激活的巨噬细胞对SGC-7901有杀伤能力,培养中加用LPS可增加激活程度以及对SGC-7901的杀伤作用。