Macrophage Chemotactic Activity Research Articles

Response toEdwardsiella ictaluriChallenge by Channel Catfish Fed Organic and Inorganic Sources of Selenium

Fingerlings of channel catfish Ictalurus punctatus (average initial weight, 1.70 g) were fed a casein-based purified diet supplemented with 0, 0.02, 0.06, 0.20, or 0.40 mg of selenium/ kg from sodium selenite (Na2SeO3), selenomethionine (Se-M), or selenoyeast (Se-Y) for 9 weeks. Subsequently, fish were challenged by immersion with a virulent strain of Edwardsiella ictaluri (105.9 cells/mL), and mortalities were recorded during a 14-d period. Antibody titers of surviving fish were measured, and macrophage chemotactic activity was determined in fish from each treatment. Dietary concentration and source of selenium significantly influenced weight gain and immune responses of the fish. Dietary selenium concentrations for maximum weight gain were 0.20 mg/kg from Se-M and Se-Y and 0.40 mg/kg from Na2SeO3. Dietary selenium concentration for maximum survival from E. ictaluri challenge was 0.20 mg/kg for fish fed Se-M and 0.40 mg/kg for fish fed Se-Y and Na2SeO3. Antibody production generally increased as dietary concentration of selenium increased. Antibody titer was highest for fish fed Se-Y, intermediate for fish fed Se-M, and lowest for fish fed Na2SeO3. Macrophage chemotactic response was the same for fish fed the control (0 selenium) and Na2SeO3 diets and was significantly lower than responses by fish fed Se-M and Se-Y. This study indicates that channel catfish challenged with E. ictaluri are responsive to dietary selenium and that organic selenium sources have greater potency than inorganic sources.

Effects of Lentinus Edodes, Grifola Frondosa and Pleurotus Ostreatus Administration on Cancer Outbreak, and Activities of Macrophages and Lymphocytes in Mice Treated with a Carcinogen, N-Butyl-N-Butanolnitrosoamine

ICR mice were treated with a carcinogen, N-butyl-N'-butanolnitrosoamine BBN), every day for 8 consecutive weeks and the effects of oral administration of edible mushrooms on the induction of urinary bladder carcinoma and on the activities of macrophages and lymphocytes were studied. Bladder carcinoma were found in all 10 mice (100%) treated with BBN alone, while we observed carcinoma only in 9 of 17 mice (52.9%), in 7 of 15 mice (46.7%) and 13 of 20 mice (65.0%) treated with Lentinus edodes, Grifola frondosa and Pleurotus ostreatus, respectively. Chemotactic activity of macrophages was suppressed in mice treated with BBN alone but maintained almost the normal level in mice treated with BBN plus Lentinus, Grifola or Pleurotus. Lymphocytes collected from mice treated with BBN plus each mushroom showed almost normal blastogenic response against concanavalin A, although those from mice treated with BBN alone completely retarded their response. Cytotoxic activity of lymphocytes against Yac-1 cells was also maintained at a normal level in mice treated with BBN plus each mushroom. Whereas in mice treated with BBN alone significant depression of NK cell activity occurred. Significantly higher cytotoxic activity against P-815 cells was observed in lymphocytes from mice treated with BBN plus each mushroom than that in lymphocytes from normal mice or mice treated with BBN alone.

Phenotypic Properties and Cytokine Production of Skin-Infiltrating Cells Obtained from Guinea Pig Delayed-Type Hypersensitivity Reaction Sites

In this study, skin-infiltrating cells were prepared from guinea pig delayed-type hypersensitivity reaction sites, and their phenotypic properties and cytokine production were examined. Our cell preparations contained around 45% nonspecific esterase-positive cells and a few skin-derived cells. Skin-infiltrating cells produced TNF activity and macrophage chemotactic activity (MCA), whereas resident skin cells produced much lower activity. The highest TNF activity was produced by skin-infiltrating cells at 2 hr after antigen injection. In contrast, a larger amount of MCA was produced by skin-infiltrating cells at 24 and 48 hr than at 2 hr after antigen injection. These kinetics were in good agreement with our previous results regarding cytokine activity in skin extracts. Gel filtration analysis and neutralization assay with a monoclonal antibody against human macrophage chemotactic factor with a molecular weight of 1 kDa (MCF-1) indicated that a guinea pig homologue of human MCF-1 was partially responsible for the MCA.

Induction of opioid receptor-mediated macrophage chemotactic activity after neonatal brain injury.

Macrophages have a prominent role in the injury response of the brain, yet the molecular mechanisms that control their invasion to the site of neuronal degeneration is unknown. After removal of the posterior cortex at birth, there is massive and specific targeting of nonresident macrophages to axotomized neurons in the lateral thalamus. The present study has identified an injury-induced, brain-derived chemotactic factor (BDCF) capable of eliciting chemotactic responses from resident peritoneal macrophages and brain macrophages. Conditioned media collected from tissue slices containing the axotomized central nervous system neurons exhibit BDCF activity. Initial experiments indicated that BDCF is a small peptide and, thus, we used specific pharmacologic reagents to characterize further BDCF activity. Naloxone, a pan opioid receptor antagonist, completely blocks BDCF activity. Although both kappa and mu opioid receptor antagonists failed to modify BDCF-induced macrophage chemotaxis, two specific delta receptor antagonists blocked BDCF. Analysis of BDCF by reverse phase HPLC and RIA revealed peak chemotactic activity in fractions consistent with the presence of an opioid peptide. The results suggest that cells in the brain respond to neuronal injury by producing and releasing opioids that can initiate a specific macrophage response.

Involvement of Inflammatory Cytokines in a Delayed-Type Hypersensitivity Reaction

We previously reported the amino acid sequence of the human macrophage chemotactic factor with a molecular weight of 1000 (MCF-1) was WLGREDGSE. In this study we examined the roles of MCF-1 and tumor necrosis factor (TNF) in a guinea pig delayed-type hypersensitivity (DTH) reaction. When macrophage chemotactic activity (MCA) in a skin extract was subjected to gel filtration, only the activity with a molecular weight of 1000 was significantly inhibited by anti-human MCF-1 mAb (7-3 mAb). Both MCA and TNF activity were detected in skin extracts from DTH inflammation sites where the specific antigen was injected. Both activities were produced at the early DTH reaction stage. In contrast, MCF-1 was produced at the late DTH reaction stage. The erythema was suppressed significantly either by anti-guinea pig TNF Ab or by 7-3 mAb, suggesting the roles of these two cytokines in a DTH reaction.

Stress and Immunity.

It is well known that immunological functions are influenced by stressors. Psychological stressors influence also usual behaviors such as eating, sleep and exercise. In this paper, we report effects of emotional behavior, restriction, sleep deprivation or nutrition on immunological functions using animal model.Using mature cats which were implanted electrode in hypothalamus, emotional behaviors such as attack and retreat were elicited by stimulation of the hypothalamus. T cell mitogen responses were significantly increased with attack, but decreased with retreat.Chemotactic activity of macrophages and number of peripheral white blood cells were almost 50% decreased by 24 hr restriction. Chemotactic activity of macrophages was suppressed by injection of ACTH at dose dependent manner in mice.Sleep deprivation for 3 days suppressed several immune functions in rats.(NZB × NZW) Fl autoimmune-prone mice which were used for animal models of systemic lupus erythematosus were compared under the influence of different calorie intakes and different calorie sources. When the energy intake was reduced to 60 % of the intake of high calorie groups, survival was doubled in fat diet group and tripled in carbohydrate diet group compared to that of high calorie groups. Immunological functions were well maintained in low calorie groups.These results indicate that immunological functions are influenced by various stressors. It depends on the period, degree and method of stressors.

Correlation between inflammatory cellular responses and chemotactic activity in bronchoalveolar lavage fluid following intratracheal instillation of nickel sulfate in rats.

In a preceding study, we reported that the numbers of macrophages and polymorphonuclear leukocytes (PMN) were increased in bronchoalveolar lavage fluid (BALF) following the intratracheal instillation of nickel sulfate (NiSO4) in rats. In the present study, BALF chemotactic activities for both macrophages and PMN were measured to investigate if the increases of these inflammatory cells in BALF depend on increases in chemotactic activities in epithelial lining fluid (ELF) of the lung. Both the number of PMN and the PMN chemotactic activity peaked at 2 days post-instillation and they were significantly correlated. However, the PMN chemotactic activity was inversely correlated with concentration of leukotriene B4 (LTB4), a well-known chemotaxin. Although PMN were not observed in control BALF, LTB4 concentration in the control ELF (ca. 5 x 10(-7) M) was estimated to have a potential to attract PMN chemotactically through a membrane in in vitro migration assay. These results suggest that the presence of LTB4 in ELF itself does not trigger transpulmonary PMN infiltration. The rat BALF were fractionated by high performance liquid chromatography (HPLC), and PMN chemotactic activity of each fraction was measured. The elution profiles of PMN chemotactic activity showed that there were at least two different chemotaxins in BALF obtained from the NiSO4-exposed rats. Macrophage chemotactic activity in BALF also peaked at 2 days post-instillation. However, the number of macrophages was not significantly correlated with the chemotactic activity for macrophage in BALF.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunomodulative effects of Chinese herbs in mice treated with anti-tumor agent cyclophosphamide

Extracts of Chinese herbs were administered with antitumor agent, cyclophosphamide (CY), and their effects on macrophages and lymphocytes were studied. Number of peritoneal macrophages significantly decreased and their chemotactic activity was suppressed by treatment with CY. Blastogenic responsiveness to Concanavalin A and NK cell activity of spleen lymphocytes were suppressed significantly in CY-treated mice. Extracts of Lithospermi radix, Astragali radix and Glycyrrhizae radix showed protective effects on immunosuppressive mice. The number of macrophages, chemotactic activity of macrophages and blastogenic response of lymphocytes were recovered to the same or more than that of normal levels. An extract of Ginseng radix showed protective effects on the number and functions of macrophages by treatment with CY but did not show any effects on the lymphocytic blastogenesis. On the contrary it showed a strong inhibitory effect on the NK cell activity. These results suggest that Chinese herbs could modulate cellular immune response, especially in the activation of macrophages and splenic lymphocytes.

IMMUNOMODULATIVE EFFECTS OF CHINESE HERBS IN MICE TREATED WITH CARCINOGEN

Extracts of Chinese herbs and their mixture “Shi-Ka-Ron” were administered with carcinogen, N-butyl-nitrosoamine (BBN), and their effects on macrophages and lymphocytes were studied. Peritoneal macrophages were significantly retarded both in their number and chemotactic activity by BBN treated. Blastogenic responsiveness to Concanavalin A of spleen lymphocytes also decreased significantly in BBN-treated mice. NK cell activity of lymphocytes was slightly suppressed by BBN treatment.Extract of Astragali radix showed protective effects on all 5 items studied. The number of macrophages and lymphocytes, and the functions of macrophages and lymphocytes maintained as same or more as normal levels in BBN plus Astragali extract-treated mice.Extract of Cnidii rhizoma showed the protective effects on the functions of macrophages and lymphocytes from BBN treatment but not on their numbers. E xtract of Lithospermi radix protected the retardation of lymphocyte function.“Shi-Ka-Ron” protected only chemotactic activity of macrophages and NK cell activity of lymphocytes but did not their numbers or blastogenic activity in spite of the mixture of herb extracts. These results suggest that the Chinese herbs may moderate each other's activity as mentioned from old time in China.

An influence of the structure of alginate on the chemotactic activity of macrophages and the antitumor activity

An influence of the structure of alginate on the chemotactic activity of macrophages and the antitumor activity

Antitumor Effector Mechanism of Interleukin‐lβ at a Distant Site in the Double Grafted Tumor System

Recombinant human interleukin‐lβ (IL‐lβ) Inhibited the growth of not only the right, but also the left non‐treated tumor in a double grafted tumor system. Since the antitumor activity of IL‐lβ against the right and left tumors was not seen in nude mice, lymphocytes have a key role in the antitumor effect of intratumoral administration of IL‐lβ. TIL (tumor‐infiltrating leukocytes) obtained from left and right side tumors treated with IL‐1β were examined by Winn assay for their antitumor activity against Meth‐A sarcoma in BALB/c mice. TIL from the right side clearly inhibited the growth of admixed Meth‐A cells, but control TIL did not. Spleen cells and right and left regional lymph node cells prepared from IL‐1‐treated mice were examined for Lyt‐1, Lyt‐2 and L3T4 phenotypes. The number of Lyt‐1‐positive lymphocytes increased in the spleen and in the right regional lymph nodes after intratumoral administration of IL‐1. Isolated tumor cells obtained from the right tumor treated with IL‐lβ and the left side tumor on day 6 were cultured in RPMI1640 with 10% fetal calf serum for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophils or macrophages. Significant neutrophil chemotactic factor and macrophage chemotactic factor activities were detected in the culture media from IL‐1‐treated tumor tissues cultured for 24 h. Neither significant neutrophil nor macrophage chemotactic activity was detected in the media from untreated tumor tissues. These results suggest that intratumoral administration of IL‐1 first induces neutrophils and macrophages in the right tumor, then Lyt‐1‐positive cells in the right regional lymph nodes and in the spleen, and subsequently induces macrophages in the left, non‐treated tumor.

Release of macrophage chemotactic activity in anaphylactic reactions in human skin

Release of macrophage chemotactic activity in anaphylactic reactions in human skin

Antitumor Effect of PSK at a Distant Site: Inductions of Interleukin‐8‐like Factor and Macrophage Chemotactic Factor in Murine Tumor

The antitumor effect of PSK, a Coriolus preparation, at a distant site was analyzed with the use of a double grafted tumor system in which male BALB/c mice received simultaneous intradermal inoculations of Meth‐A tumor in the right (106 cells) and the left (2 × 105 cells) flanks and were then injected with PSK in the right tumor on the third day thereafter. The antitumor effect of intratumoral administration of PSK in the right tumor on days 3, 4 and 5 was compared with the effect of surgical resection of the right tumor on day 5. Three out of 8 mice given PSK intratumorally became tumor‐free whereas no mouse tumor‐free in the left flank was found among the surgically resected mice. As regards sinecomitant immunity, tumor inoculation into the right flank followed by intratumoral administration of PSK on days 3 and 5 and surgical excision of the primary tumor on day 6 resulted in complete rejection of a tumor challenge in the left flank on day 21. The combination of presurgical intratumoral injections of PSK (more than 2 times) and postoperative oral administration of PSK appeared to be most effective in eradicating secondary tumors. Isolated TILs (tumor‐infiltrating lymphocytes), obtained from the right tumor (treated with PSK) and the left tumor on day 10 in the double grafted tumor system were cultured in RPMI1640 with 10% fetal calf serum for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophils or macrophages. Significant neutrophil chemotactic factor (NCF) and macrophage chemotactic factor (MCF) activities were detected in the culture media from PSK‐treated TILs that had been cultured for 24 h. Neither significant neutrophil nor macrophage chemotactic activity was detected in the media from untreated TILs. NCF and MCF activities were also detected in the culture supernatant from PSK‐treated tumor tissue on day 6. PSK‐induced NCF in the murine tumor was neutralized by treatment with anti‐human IL‐8 IgG, and might be murine IL‐8‐like factor. Therefore, neutrophil and macrophage infiltrations of tumors following intratumoral injections of PSK are probably mediated by inductions of IL‐8‐like factor and MCF.

Chemotactic factors for macrophages produced in inflamed skin.

A newly discovered macrophage-chemotactic factor (MCFS-1) was extracted and purified (488-fold) from skin sites of guinea pigs showing delayed hypersensitivity to bovine gamma-globulin. MCFS-1 is a heat-labile glycoprotein with a molecular weight of 150,000, consisting of two polypeptide chains. It has in vivo as well as in vitro chemotactic activity for macrophages and shared 50% of the chemotactic activities for macrophages in the extract. It is produced by limited proteolysis of endogenous trypsin-like protease(s) of plasma precursor protein (Pre-MCFS-1). Enzyme immunohistochemistry reveals that Pre-MCFS-1 is produced in the liver and distributed in the normal skin as a proinflammatory factor. ELISA reveals that the concentrations of the factor are: 140 micrograms/ml in plasma, 7.1 micrograms/ml in inflamed skin extract, and 2.8 micrograms/ml in normal skin extract.

Inhibition of the accumulation of macrophages and the generation of macrophage chemotactic activity by dexamethasone in concanavalin A-induced peritonitis of mice.

A delayed-type inflammatory response was evoked in mice using concanavalin A (Con A) as a stimulus, and the effect of various anti-inflammatory agents on the inflammation was examined. The intraperitoneal injection of Con A in the mouse resulted in the marked accumulation of leukocytes, especially macrophages, in the peritoneal cavity between 16 and 48 hr after the injection. Prior to the accumulation of macrophages, the chemotactic activity for macrophages appeared in the peritoneal fluid, and was associated with protein(s) in the molecular weight range from 10,000 to 100,000 daltons. When the effect of various agents on Con A-induced peritonitis was examined, neither anticomplementary agents (FUT-175 and K-76 COONa), bromophenacyl bromide, nordihydroguaiaretic acid nor indomethacin affected the generation of chemotactic activity and the accumulation of macrophages, suggesting that C5a, prostaglandins and leukotriene B4 are hardly involved in the Con A-induced macrophage accumulation. On the other hand, dexamethasone suppressed both the generation of chemotactic activity and the accumulation of macrophages. Taking into consideration the observation that the synthesis of macrophage chemotactic factors by mitogen-stimulated lymphocytes is inhibited by glucocorticoids, these results suggest that the macrophage chemotactic lymphokines might be involved in the accumulation of macrophages in Con A-induced peritonitis.

Influence of toxic chemicals on the chemotactic response of fish macrophages

The chemotactic efficiency of macrophages isolated from the kidney of spot, Leiostomus xanthurus, and hogchoker, Trinectes maculatus. was determined in fish captured from the York River and the heavily polluted Elizabeth River (Virginia). Chemotactic activity was quantified in Boyden chambers using Escherichia coli as the chemotactic stimulus. Macrophage chemc‐taxis was found to be markedly reduced in the Elizabeth River fish as compared to York River controls. Chemotactic migrations of macrophages at 90 min were 55% and 33% for control and experimental spot, respectively. Values for control and experimental hogchoker were 85% and 56%, respectively. The macrophage chemotactic activity of Elizabeth River fish returned to normal (spot, 56%; hogchoker, 80%) after the fish were held in clean water for 3 weeks. This indicates that the decreased chemotactic activity was related to exposure to Elizabeth River pollutants but may be reversible.

A new method of eliciting delayed hypersensitivity in the mouse abdominal cavity

A new method of determining delayed hypersensitivity quantitatively was investigated in mice. Mice were sensitized with 150 μg of ferritin and, 3 weeks later, antigen challenge was performed by implanting a sponge containing antigen in the abdominal cavity. Cells accumulated in the sponge markedly increased in number for 24–72 h after the challenge; mononuclear cells predominated by 48 h. When sensitized lymphocytes were transferred passively to a normal recipient, marked cell accumulation in the sponge was found 48 h after the challenge. Immunological specificity was confirmed in animals sensitized to antigen and receiving passive transfer of sensitized cells. Strain differences in this reaction were observed. Cortisone (20 mg/kg for 6 days before challenge) significantly decreased cell accumulation. Delayed hypersensitivity was also elicited in the ear of sensitized animals. Extracts of sponges removed from antigen-challenged mice had macrophage chemotactic activity.

Macrophage activity in mice undergoing chronic graft-versus-host reactions.

The functional state of the mononuclear phagocyte system has been investigated in mice undergoing chronic graft-versus-host (GVH) reactions (GVHR), initiated by the injection of parental DBA/2 lymphoid cells into (DBA/2 X C57BL/6)F1 hybrid mice. Macrophage function was assessed in vivo by the ability to develop host resistance to infection with Listeria monocytogenes and found to be normal in GVH mice, as measured by the development of resistance during the early phase of natural (macrophage-mediated) resistance to the infection. During the later phase of acquired immunity to listerial infection, GVH mice had lowered resistance, but this was attributed to impaired T cell immunity rather than to defective macrophage function. The inflammatory response to a phlogistic agent, thioglycolate, was also found to be normal in GVH mice, as measured by the accumulation of inflammatory macrophages in the peritoneal cavity. In an in vitro assessment of macrophage function, phagocytosis was found to be enhanced initially (2 weeks following GVHR induction) but it subsequently became depressed for the duration of the study (12 weeks after GVHR induction). Macrophage chemotactic activity was initially normal, then became depressed and remained so for the duration of the study. Thus, despite the profound suppression of specific immunity induced by the GVH reaction and the functional defects of GVH macrophages apparent in vitro, the response of the mononuclear phagocyte system to in vivo stimuli, such as infection or inflammation, is unimpaired in GVH mice.

Effect of oral administration of a variety of bacteria on depressed macrophage functions in tumour-bearing rats

In consideration of the well documented influence of normal microbial flora on the level of activation of macrophages, we evaluated the effects of oral administration of bacteria on rats with depressed macrophage functions. An oral, killed polyvalent vaccine (Diplococcus pneumoniae types I, II and III, Streptococcus haemolyticus, Staphylococcus aureus and Haemophilus influenzae), the live lyophilized Streptococcus faecium and spores of Bacillus subtilis, respectively, were administered orally to immuno-depressed rats. Results demonstrate the restoration of phagocytosis, intracellular killing and the chemotactic activity of macrophages. These experimental observations suggest that bacterial flora associated with mucosae can influence the level of activation of peritoneal macrophages.

A C5-derived macrophage chemotactic factor from DNP-Ascaris extract-induced skin lesion in guinea pigs.

In complement-depleted condition induced by cobra venom factor (CoF), tissue macrophage reaction and macrophage chemotactic activity (MCA) in skin extract from skin lesions induced by DNP-Ascaris extract (DNP-As) were decreased, respectively. MCA in the fraction containing macrophage chemotactic factor b (B fraction) was decreased completely. While MCA in the fraction containing macrophage chemotactic factor a and c (A fraction) was affected only slightly. These results suggested that the decrease of MCA of B-fraction might be associated with depletion of complement system by CoF. Using anti-C5 antibody, it was confirmed that macrophage chemotactic factor-b (MCF-b) (MW 14,000: thermostable) might be derived from C5 fragment in vivo.