Enhancement of lymphocyte blastogenesis and neutrophil function by avridine in dexamethasone-treated and nontreated cattle

The lipoidal amine, N,N-dioctadecyl-N',N'-bis (2-hydroxyethyl) propanediamine (avridine or CP 20,961), formulated in liposomes, was evaluated for its effect on leukocyte kinetics, lymphocyte blastogenesis, and polymorphonuclear leukocyte (PMN) function in dexamethasone-treated and nontreated cattle. In the 1st experiment, cattle were given avridine in a single IM injection of 0.1, 1.0, or 10 mg/kg of body weight. All doses induced swelling at the injection site, a febrile response, and a leukocytosis due to a neutrophilia. Mononuclear cell numbers were normal. All 3 groups of avridine-treated animals had a higher mean lymphocyte blastogenic response to mitogens on the 4 days after administration than did the control nontreated animals. Avridine administration was associated with an enhanced ability of PMN to ingest Staphylococcus aureus and to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). The highest dose (10 mg/kg) was associated with a depression of the ability of PMN to iodinate protein. An effect of avridine on PMN random migration under agarose or nitroblue tetrazolium (NBT) reduction was not observed. In a 2nd experiment, cattle were given no treatment, 0.04 mg of dexamethasone/kg IM, or 10 mg of avridine/kg IM followed 24 hours later by 0.04 mg of dexamethasone/kg. Dexamethasone administration caused a leukocytosis due to a neutrophilia with normal mononuclear cell numbers, an enhancement of PMN random migration under agarose, and an inhibition of NBT reduction, iodination, and ADCC activity of PMN. Dexamethasone did not have a detectable effect on lymphocyte blastogenesis or on ingestion of S aureus by PMN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alteration of neutrophil function associated with coccidiosis in cattle: influence of decoquinate and dexamethasone

Twenty Holstein steers subclinically infected with coccidia were allotted to 2 groups of 10 steers each. One group received a diet containing 0.5 mg of decoquinate/kg of body weight. After 25 days on the diet, there was no difference between the groups in lymphocyte blastogenic responsiveness to mitogens; however, there were differences in neutrophil function. Lymphocytes from steers of the decoquinate-fed group had decreased random migration under agarose, enhanced cytochrome C reduction, and enhanced iodination activity. Other measures of neutrophil function evaluated (chemotactic index, Staphylococcus aureus ingestion, and antibody-dependent and -independent cell-mediated cytotoxicity) were not affected. After 30 days of decoquinate feeding, half of the cattle in each group received 5 daily IM injections of dexamethasone (0.04 mg/kg of body weight). The dexamethasone-treated steers from the group that did not have decoquinate in the diet developed clinical coccidiosis, whereas the decoquinate-treated steers remained clinically normal. Lymphocyte and neutrophil function were again evaluated for a 3-day period beginning 4 days after dexamethasone treatment was halted. Neutrophils from the steers that developed clinical coccidiosis after dexamethasone administration had significantly (P less than 0.05) inhibited random migration under agarose, cytochrome C reduction, and iodination activity, but significantly (P less than 0.01) enhanced S aureus ingestion. The feeding of decoquinate prevented the inhibition of neutrophil cytochrome C reduction and lessened the inhibition of neutrophil iodination in the dexamethasone-treated group. Dexamethasone treatment was associated with an inhibition of lymphocyte blastogenic responsiveness to phytohemagglutinin in principals as well as controls.     

Suppression of neutrophil and lymphocyte function induced by a vaccinal strain of bovine viral diarrhea virus with and without the administration of ACTH

Effects of a modified live vaccine (MLV) strain of bovine viral diarrhea virus (BVD) on lymphocyte and neutrophil function were determined in cattle with and without increased plasma cortisol (hydrocortisone) concentrations. Cattle were given MLV-BVD vaccine IM and intranasally. Cattle given ACTH received 200 IU every 12 hours for 10 doses. The MLV-BVD virus when administered alone caused no apparent clinical signs or body temperature response. Of 4 MLV-BVD-treated calves that were also given ACTH, 2 developed increased body temperature and respiratory distress. The MLV-BVD virus caused a decrease in circulating lymphocytes and neutrophils, whereas administration of ACTH and MLV-BVD induced a neutrophilia and lymphopenia. The MLV-BVD virus and ACTH when administered separately or in combination caused a depression of lymphocyte blastogenesis in response to selected mitogens. Neutrophils were separated from the peripheral blood and their function was evaluated, using the following procedures: (i) random migration under agarose, (ii) ingestion of 125I-labeled Staphylococcus aureus, (iii) quantitative nitroblue tetrazolium reduction, (iv) iodination, and (v) antibody-dependent cell-mediated cytotoxicity (ADCC). The MLV-BVD virus produced a significant (P less than 0.05) suppression of neutrophil iodination and ADCC. Neutrophils from cattle given MLV-BVD virus and ACTH had enhanced random migration, enhanced S aureus ingestion, suppressed iodination, and suppressed ADCC activity.     

Effects of dexamethasone, levamisole, and dexamethasone-levamisole combination on neutrophil function in female goats

Effects of dexamethasone, levamisole, or combined dexamethasone-levamisole administration on polymorphonuclear neutrophil (PMN) function in healthy, adult female goats were studied. Goats were assigned to treated (n = 6) and control (n = 6) groups. In experiment 1, treated goats were given levamisole (6 mg/kg of body weight, IM). In experiment 2, treated goats were given 0.1 mg of dexamethasone/kg, IV, for 3 consecutive days, 1 mg of dexamethasone/kg, IV, for 6 consecutive days, and 6 mg of levamisole/kg, IM, with a 4th injection of 1 mg of dexamethasone/kg. All injections were administered 12 hours before blood collection. The PMN were evaluated for random migration and chemotaxis under agarose, ingestion of Staphylococcus aureus, cytochrome C reduction, iodination, and antibody-dependent cell-mediated cytotoxicity. Levamisole alone did not alter the function of caprine PMN. Both doses of dexamethasone caused increased random migration and decreased cytochrome C reduction and iodination. Dexamethasone resulted in no changes in chemotaxis, S aureus ingestion, and antibody-dependent cell-mediated cytotoxicity. Random migration and cytochrome C reduction returned toward base line in cells from dexamethasone and levamisole-treated goats. Although iodination activity in cells from dexamethasone-treated goats remained significantly (P less than 0.05) lower than those of controls after levamisole administration, a rebound toward base-line activity occurred.     

Effect of levamisole on lymphocyte blastogenesis and neutrophil function in dexamethasone-treated cattle

Levamisole was evaluated at 6 dose levels for its ability to prevent the dexamethasone-induced suppression of in vitro lymphocyte blastogenesis or neutrophil function in cattle. Dexamethasone (0.4 mg/kg of body weight, IM) and levamisole hydrochloride (0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg orally) were administered to groups of 4 cattle daily for 3 days. Another group of 4 cattle were given the 3-day dexamethasone treatment and 6.0 mg/kg of levamisole (the recommended anthelmintic dose) was given only once on the 1st day that dexamethasone was given. Results obtained from the dexamethasone-levamisole-treated cattle were compared with results obtained from cattle that were given only dexamethasone. Levamisole had no apparent consistent ability to enhance lymphocyte blastogenic responsiveness (to the mitogens phytohemagglutinin, concanavalin A, or pokeweed mitogen or in a 1-way mixed lymphocyte reaction) or to enhance neutrophil function (random migration, nitroblue tetrazolium reduction, iodination, or antibody-dependent cell-mediated cytotoxicity) in dexamethasone-treated cattle.     

Influence of recombinant human interleukin-2 administration on lymphocyte and neutrophil function in clinically normal and dexamethasone-treated cattle

Recombinant human interleukin-2 (rhIL-2) was evaluated for its influence on total and differential WBC counts, lymphocyte blastogenic responsiveness to mitogens, and several measurements of neutrophil function in clinically normal and in dexamethasone-treated cattle. A single dose of rhIL-2 (2.5 X 10(7) U) given SC had no influence on the total or differential WBC count; however, it did cause an inhibition of neutrophil random migration. The other measurements of neutrophil function (Staphylococcus aureus ingestion, cytochrome C reduction, iodination, and antibody-dependent and antibody-independent cell-mediated cytotoxicity) evaluated were not significantly altered. The rhIL-2 treatment was associated with a significant (P less than 0.01) decrease in uptake of [3H]thymidine in unstimulated lymphocytes and a tendency toward enhanced blastogenesis of lymphocytes stimulated with phytohemagglutinin. This enhancement was significant (P less than 0.05) only when the results were expressed as a stimulation index. Lymphocyte responsiveness to concanavalin A and pokeweed mitogen was not significantly influenced by rhIL-2 administration. Dexamethasone (0.04 mg/kg) administered every 24 hours for 3 consecutive days altered the WBC count and several measurements of lymphocyte and neutrophil function. The administration of a single dose of rhIL-2 (2.5 X 10(7) U) 8 hours after the first dose of dexamethasone did not alter the influence of dexamethasone on any of the measurements. These results indicated that rhIL-2 has some biologic activity in cattle, but when used as administered here, did not overcome the influence of dexamethasone on the in vitro measurements of lymphocyte and neutrophil function that were evaluated.     

Influence of arachidonic acid metabolites and steroids on function of bovine polymorphonuclear neutrophils.

Polymorphonuclear neutrophils (PMN) from 4 ovariectomized healthy cows were incubated with 0 (control), 10(-8), 10(-7), and 10(-6) M arachidonic acid metabolites of the cyclo- and lipoxygenase pathways for 30 minutes, and with steroids for 2 hours. Immediately after incubation, PMN were subjected to the following function assays: chemotaxis against zymosan-activated serum, chemotaxis against arachidonic acid metabolite or steroid at the doses given (only control PMN were tested), random migration, ingestion of 125I-iododeoxyuridine-labeled Staphylococcus aureus (125I-IdUR-S aureus), iodination of proteins, cytochrome C reduction, antibody-independent and -dependent cell-mediated cytotoxicity (AICC and ADCC). Prostaglandin F2 alpha was chemoattractant and stimulated ingestion of 125I-IdUR-S aureus. Prostaglandin E2 stimulated cytochrome C reduction, whereas prostacyclin inhibited iodination of proteins. Thromboxane B2 stimulated ADCC. Leukotriene B4 was chemoattractant for bovine PMN and stimulated random migration and AICC. 5-Hydroxyeicosatetraenoic acid was also chemoattractant, but inhibited ingestion of 125I-IdUR-S aureus. 15-Hydroxyeicosatetraenoic acid was chemoattractant and decreased ADCC. Lipoxin A4 stimulated random migration, whereas lipoxin B4 inhibited chemotaxis against zymosan-activated serum, but was chemoattractant and stimulated cytochrome C reduction. 12-Hydroxyhepadecatrienoic acid and 12-hydroxyeicosatetraenoic acid did not influence any of the PMN functions tested. Of the steroids tested, cortisol increased ADCC, and progesterone stimulated cytochrome C reduction, but decreased ADCC. 17 beta-Estradiol and estrone were chemoattractant and stimulated cytochrome C reduction. In addition, estrone also stimulated random migration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation of bovine neutrophils by recombinant bovine tumor necrosis factor-alpha

The in vitro effect of bovine recombinant tumor necrosis factor-alpha (rbTNF-alpha) on bovine neutrophil function and the possibility that rbTNF-alpha and recombinant bovine interferon-gamma (rbIFN-gamma) act synergistically were investigated. Treatment of neutrophils with rbTNF-alpha (0.05 micrograms/ml; approximately 50 U/ml) at 37 degrees C for 2.5 h resulted in enhancement of antibody independent neutrophil-mediated cytotoxicity (AINC) and inhibition of random migration and chemotaxis. The same treatment resulted in a slight decrease in iodination and cytochrome C reduction, but did not affect Staphylococcus aureus ingestion, or antibody dependent cell-mediated cytotoxicity. Kinetic and inhibitor studies indicated that the action of rbTNF-alpha was rapid and was independent of protein and RNA synthesis by neutrophils. Evaluation of the synergistic activities of rbTNF-alpha and rbIFN-gamma indicated that treatment of neutrophils with these two cytokines simultaneously resulted in additive enhancement of AINC and inhibition of random migration and chemotaxis. There was no additive effect of the two cytokines on inhibition of iodination or cytochrome C reduction.     

Defective function of leukocytes from cattle persistently infected with bovine viral diarrhea virus, and the influence of recombinant cytokines.

Cattle persistently infected with bovine viral diarrhea (BVD) virus have decreased neutrophil and lymphocyte functions. We reevaluated these functions and further characterized the inhibition of persistent BVD virus infection in neutrophils, using sensitive kinetic assays. In addition, the influence of in vitro incubation of neutrophils with recombinant bovine interferon gamma (rBoIFN gamma) and in vitro incubation of lymphocytes with recombinant bovine interleukin-2 was evaluated. Significant (P less than 0.05) decrease in random migration under agarose, Staphylococcus aureus ingestion, cytochrome-C reduction, iodination, antibody-independent cell-mediated cytotoxicity, oxidant production, and cytoplasmic calcium flux were observed in neutrophils from cattle persistently infected with BVD virus, compared with noninfected control cattle. Incubation of neutrophils from noninfected controls with rBoIFN gamma significantly (P less than 0.05) decreased random migration under agarose, cytochrome-C reduction, and cytoplasmic calcium flux. Neutrophils from cattle persistently infected with BVD virus also had decreased random migration under agarose after incubation with rBoIFN gamma; in addition, antibody-independent cell-mediated cytotoxicity, elastase release, and cytoplasmic calcium flux were significantly enhanced. The rBoIFN gamma induced significantly (P less than 0.05) different effects on chemotaxis, cytochrome-C reduction, iodination, and cytoplasmic calcium flux of neutrophils from infected and control cattle. The rBoIFN gamma was more effective at improving the function of neutrophils from cattle persistently infected with BVD virus, compared with neutrophils from controls. Lymphocytes from infected cattle had decreased blastogenesis in response to phytohemagglutinin, concanavalin A, and pokeweed mitogen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations in bovine neutrophil function during the periparturient period

Neutrophils from 8 Holstein heifers were evaluated for function during the periparturient period. Random migration, ingestion of bacteria, superoxide anion production, native (nonenhanced) chemiluminescence, iodination, and antibody-dependent, cell-mediated cytotoxicity by neutrophils were determined. Foremilk samples were evaluated for bacteria. Significant (P less than 0.05) increases in random migration of neutrophils, iodination, and chemiluminescence were evident 2 weeks before parturition and then decreased dramatically by the first week after parturition. These impairments of neutrophil function after parturition may be manifested as a severe cumulative deficit in the native defenses afforded by the neutrophil.     

Functional and ultrastructural evaluation of neutrophils from foals and lactating and nonlactating mares

Neutrophils from 4 pony foals, 3 lactating pony mares, and 3 nonlactating mares were evaluated ultrastructurally and by in vitro function tests. Neutrophils from foals had significantly (P = 0.05) less random migration than neutrophils from mares; values in tests for iodination and Staphylococcus aureus ingestion were also lower with foal neutrophils. Neutrophils from lactating mares had lower responses to iodination, antibody-dependent cell-mediated cytotoxicity, and random migration tests than did neutrophils from nonlactating mares. Ultrastructurally, granule concentration did not differ significantly among groups. A slight decrease in primary granules and a corresponding increase in granules with a flocculent matrix indicates partial spontaneous neutrophil degranulation in foals and lactating mares.     

Altered protein expression in neutrophils of calves treated with dexamethasone

The effect of glucocorticoid treatment on protein expression in bovine neutrophils was examined with a proteomic approach to address the mechanisms by which stress alters neutrophil function and predisposes to bacterial pneumonia in cattle. Calves 6 to 8 mo old were treated with dexamethasone (0.1 mg/kg), neutrophils were isolated 24 h later, and whole-cell lysates were examined by 2-dimensional electrophoresis. Differentially expressed protein spots were identified by peptide mass fingerprinting. The antimicrobial protein lactotransferrin was detected at increased amounts in the neutrophils of the dexamethasone-treated calves. Proteins detected at reduced amounts in the neutrophils of the dexamethasone-treated calves included annexin 1, phosphoglycerate mutase, Na(+) - K+ ATPase, and cathelicidin 1. These findings identify glucocorticoid-induced changes in the levels of neutrophil proteins involved in host defense, inflammation, and cellular metabolism and suggest additional mechanisms by which glucocorticoids affect neutrophil function.     

Effects of infection with parainfluenza-3 virus and infectious bovine rhinotracheitis virus on neutrophil functions in calves

Calves were challenge exposed in separate experiments with parainfluenza-3 (PI-3) virus or infectious bovine rhinotracheitis (IBR) virus. Blood neutrophils were assayed for functional activity every other day for at least 3 weeks by random migration, Staphylococcus aureus ingestion, antibody-dependent cell-mediated cytotoxicity, cytochrome-c reduction, iodination, and native chemiluminescence. Exposure to PI-3 virus resulted in a brief febrile response and no other clinical signs. Alterations in total or differential WBC counts were not detected. Chemiluminescence and iodination activities were reduced from activities before exposure. Exposure to IBR virus resulted in mild clinical signs and a febrile response of several days' duration. Total WBC and mononuclear cell counts were reduced. Random migration was reduced, whereas S aureus ingestion was enhanced. We concluded that infection of calves with IBR virus and PI-3 virus might directly or indirectly result in alterations of neutrophil function. The functional alterations apparently are different for each virus. These virus-induced alterations in neutrophil function might predispose calves to secondary bacterial pneumonia.     

Function of neutrophils and chemoattractant properties of fetal placental tissue during the last month of pregnancy in cows.

Neutrophils were isolated from the blood of pregnant cows on days 255, 265, and 275 of pregnancy, and on the day of parturition (n = 5/group), and in addition, simultaneously from 4 ovariectomized healthy cows (control animals). Neutrophils were subjected to neutrophil function assays (chemotaxis against zymosan-activated serum, random migration, ingestion of 125I-iododeoxyuridine [IdUR]-labeled Staphylococcus aureus, iodination of proteins, cytochrome C reduction, antibody-independent and antibody-dependent cell-mediated cytotoxicity). Results were expressed as percentage of control animals. Fetal placental tissue (cotyledon), uterine wall tissue, and skeletal muscle were obtained from the principal animals on the aforementioned days via laparotomy, and tissue suspensions were prepared. Chemotaxis of neutrophils was tested against tissue supernatants. Compared with day 255, there was an increase in ingestion of 125I-IdUR-S aureus at parturition, whereas iodination of proteins and cytochrome C reduction were reduced on the day of calving. The other neutrophil functions tested did not change over time of gestation. Fetal placental and uterine wall tissue attracted neutrophils with uterine wall tissue having a tendency to be more potent than cotyledonary tissue. Skeletal muscle tissue did not attract neutrophils. There was no change in chemotaxis response of neutrophils evoked by intrauterine and uterine tissues over time of gestation. It was concluded that at parturition, neutrophil function is impaired with respect to their bactericidal effects, which may render the animal more susceptible to bacterial infections, and that the chemoattractant properties of fetal placental and uterine wall tissues are tissue-specific, at least when compared with skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Depression of polymorphonuclear leukocyte function associated with experimentally induced Escherichia coli mastitis in sows

In a study of susceptibilities of sows from 2 herds to experimentally induced Escherichia coli mastitis, a marked difference was seen. The "susceptible" sows were from a conventional herd and "resistant" sows were from a specific-pathogen-free herd. The purpose of the study was to determine whether deficient neutrophil function was associated with increased susceptibility to E coli-induced mastitis. Four in vitro procedures were used to evaluate polymorphonuclear leukocyte (PMN) function: (i) random migration under agarose, (ii) ingestion of 125I-iododeoxyuridine-labeled Staphylococcus aureus, (iii) quantitative nitroblue tetrazolium reduction, and (iv) iodination. After parturition and intramammary inoculation with E coli, sows from the susceptible herd were neutropenic and the neutrophils which were present in the peripheral blood had reduced function. Specifically, there were depressed random migration under agarose, S aureus ingestion, and iodination when compared with PMN function in resistant sows. These data indicate that susceptibility to E coli mastitis was associated with deficiencies in PMN numbers and function. Potential causes of the neutrophil dysfunction are discussed and include possible systemic hormonal aberrations or the presence of an inapparent viral or bacterial infection.     

Influence of conditioned media from bovine cotyledon tissue cultures on function of bovine neutrophils.

Bovine fetal placental (cotyledon) tissue obtained from pregnant cows on days 255, 265, and 275 of gestation, as well as immediately after parturition (n = 5) was incubated in media for 48 hours, and the incubation media were collected. Neutrophils from 4 ovariectomized nonpregnant cows were incubated for 2 hours with conditioned media from placental tissue cultures or medium (control). Immediately after incubation, the neutrophils were subjected to the following leukocyte function assays: chemotaxis against zymosan-activated serum, chemotaxis against undiluted conditioned media (only neutrophils that were incubated in medium only), random migration, ingestion of 125I-iododeoxyuridine Staphylococcus aureus (125I-IdUR-S aureus), iodination of proteins, cytochrome C reduction, and antibody-independent and -dependent cell-mediated cytotoxicity. Conditioned media from cultured cotyledon tissue was chemoattractant for bovine neutrophils, and increased chemotactic response of neutrophils against zymosan-activated serum by 13%. The following neutrophil functions were decreased: random migration by 25%, iodination of proteins by 44%, cytochrome C reduction by 13%, and antibody-dependent cell-mediated cytotoxicity by 5%. Ingestion of 125I-IdUR-S aureus and antibody-independent cell-mediated cytotoxicity were not influenced by coincubation of neutrophils and conditioned media. Time of gestation did not alter the effects of conditioned media on neutrophil function. It was concluded that chemotactic properties of cotyledon tissue extracts, as has been reported earlier, may be attributable to substances released by fetal placental tissue. Those substances might also locally or systemically influence the oxygen-dependent antimicrobial system of neutrophils, thereby causing an increased susceptibility to bacterial infections in the peripartum period.     

Neutrophil function in dogs with congenital ciliary dyskinesia.

In vitro neutrophil function was assessed in two English Springer Spaniel dogs, two Bichon Frise dogs, and one Chow Chow dog with congenital ciliary dyskinesia; three clinically normal English Springer Spaniel dogs that were presumed heterozygous for congenital ciliary dyskinesia; and five control dogs. Chemotaxis and random migration in affected and heterozygous dogs were found to be comparable to those of control dogs. Increased (P less than or equal to 0.05) neutrophil adhesion, antibody dependent cell-mediated cytotoxicity, iodination of proteins, and oxygen radical production in neutrophils from affected dogs were probably the result of chronic bacterial infection in vivo. Bacterial ingestion by neutrophils from the three heterozygous English Springer Spaniel dogs was significantly increased compared to control dogs but was not different from affected English Springer Spaniel dogs, suggesting a breed-related phenomenon. Significant decreases in neutrophil function were not seen in any of the dogs with congenital ciliary dyskinesia, indicating that a defective microtubular system is not shared by respiratory cilia and neutrophils and that defective neutrophil function does not contribute to respiratory infection.     

Opsonin-dependent stimulation of bovine neutrophil oxidative metabolism by Brucella abortus

Nonopsonized Brucella abortus and bacteria treated with fresh antiserum, heat-inactivated antiserum, or normal bovine serum were evaluated for their ability to stimulate production of superoxide anion and myeloperoxidase-mediated iodination by neutrophils from cattle. Brucella abortus opsonized with fresh antiserum or heat-inactivated antiserum stimulated production of approximately 3 nmol of O2-/10(6) neutrophils/30 min. Similarly treated bacteria also stimulated the binding of approximately 4.3 nmol of NaI/10(7) neutrophils/h to protein. Significant (P less than 0.05) production of O2- and iodination activity by neutrophils were not stimulated by nonopsonized bacteria or organisms treated with normal bovine serum. Seemingly, B abortus stimulated oxidative metabolism in bovine neutrophils; however, the stimulation was dependent on the presence of bacterial associated opsonins.     

Alteration of neutrophil function in BCG-treated and non-treated swine after exposure to Salmonella typhimurium.

Salmonella typhimurium infection in swine causes an enterocolitis followed by a persistent carrier state, but little is known about the mechanisms that allow this organism to colonize and persist in host tissues. Neutrophils provide a first line of defense against invading pathogens such as Salmonella typhimurium. The purpose of this study was to evaluate porcine neutrophil function after in vivo exposure to Salmonella and to determine if the immunomodulator, bacillus Calmette Guerin (BCG), exerts any effect on neutrophil function or on the colonization and persistence of S. typhimurium in the pig. Compared to negative controls, neutrophils from pigs exposed to S. typhimurium exhibited significantly decreased iodination, cytochrome-C reduction, antibody-dependent cell-mediated cytotoxicity, random migration, and chemotaxis (P less than or equal to 0.05). Neutrophil bactericidal activity against S. typhimurium was significantly enhanced. Most of the significant differences were noted in the first two days after exposure to Salmonella. Often the functional alterations were biphasic, peaking again 7-10 days after exposure. BCG alone significantly depressed random migration and cytochrome-C reduction in unstimulated neutrophils. The clinical course, colonization pattern, and persistence of Salmonella were similar between pigs receiving BCG and untreated pigs. These data suggest that S. typhimurium infection causes a depression in oxidative metabolism and motility, yet an increase in overall bactericidal activity against S. typhimurium in circulating porcine neutrophils. It also appears that BCG treatment, as reported here, does not enhance resistance of pigs to S. typhimurium colonization or reduce the number of persistent organisms in the porcine ileum.     

Lymphocyte blastogenesis and neutrophil function in cattle persistently infected with bovine viral diarrhea virus

Neutrophil function and mononuclear cell proliferative responses to mitogens were determined in healthy cattle and in cattle persistently infected with bovine viral diarrhea (BVD) virus. Uptake of [3H]thymidine by resting and mitogen-stimulated peripheral blood mononuclear cells was significantly lower in cattle persistently infected with BVD virus than in healthy cattle. Neutrophils from cattle persistently infected with BVD virus had significantly impaired capability to ingest Staphylococcus aureus, but were normal in respect to random migration under agarose, cytochrome C reduction, iodination, and antibody-dependent cell-mediated cytotoxicity. Impairment of neutrophil function in cattle persistently infected with BVD virus differs from impairment of neutrophil function reported in healthy cattle mounting an immune response to recent BVD virus infection.