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1.
In order to explore the building conditions of acute lung injury, healthy Kunming mice were selected, by intraperitoneal injection of cascade dose of LPS (0, 2, 4, 6, 8, 10 mg/kg) to observe the mice respiratory frequency, mortality, lung W/D value and the changes of tissue structure in different conditions, and detect the expression changes of inflammation cytokine, IL-10,TNF-α, IL-1β and IFN-γ. The results showed that compared with control group, lung W/D value in 4 mg/kg LPS group significantly increased (P<0.05) and lung W/D values in 6, 8 and 10 mg/kg LPS groups extremely significantly increased (P<0.01). Pathological analysis showed that 6 mg/kg LPS group appeared lung congestion, alveolar luminal and pulmonary interstitial exudation, alveolar septal thickening, and a small amount of neutrophil infiltration. 8 and 10 mg/kg LPS groups appeared pulmonary congestion, alveolar and pulmonary interstitial exudation, alveolar septal thickening and neutrophil infiltration. Compared with control group, collagen fibers of the lung tissue in 6, 8, 10 mg/kg LPS group increased, and more appeared in the lung around the trachea, 10 mg/kg LPS group was the most obvious. The inflammatory factors in 2, 4, 6, 8 and 10 mg/kg LPS groups had extremely significantly increased compared with control group (P<0.01). Pathological biopsy and related indicators showed that the model of mice could be successfully constructed by intraperitoneal injection of 8 mg/kg LPS for 12 h.  相似文献   

2.
为探究构建急性肺损伤模型的条件,本试验选用健康昆明小鼠,经腹腔注射递增剂量脂多糖（LPS）（0、2、4、6、8、10 mg/kg）,观察不同条件下小鼠呼吸频率、死亡率、肺脏干湿重比值及组织结构变化,检测炎症因子IL-10、TNF-α、IL-1β及IFN-γ在不同程度肺损伤中的表达量变化。结果显示,4 mg/kg LPS组肺脏干湿重比值显著高于对照组（P<0.05）;6、8和10 m/kg LPS组肺脏干湿重比值极显著高于对照组（P<0.01）。病理切片分析显示,6 mg/kg LPS组小鼠肺脏出现充血,肺泡腔及肺间质出现渗出,肺泡隔增厚,出现少量中性粒细胞浸润;8、10 mg/kg LPS组小鼠肺脏充血明显,肺泡腔及肺间质出现渗出,肺泡明显隔增厚,出现中性粒细胞浸润;与对照组相比,6、8、10 mg/kg LPS组肺组织中胶原纤维大量增多,且多出现在肺气管周围,10 mg/kg LPS组现象最明显。炎症因子检测分析结果显示,与对照组相比,2、4、6、8、10 mg/kg LPS组炎症因子均极显著增加（P<0.01）。结合病理组织切片及相关检测指标表明,昆明小鼠腹腔注射8 mg/kg LPS并作用12 h,可成功构建急性肺损伤模型。  相似文献   

3.
Interleukin-8 (IL-8), an in vitro and in vivo neutrophil chemoattractant, is expressed at high levels in the lesions observed in bovine pneumonic pasteurellosis. Because of the role of neutrophils in the pathogenesis of pneumonic pasteurellosis, we investigated the relative importance of IL-8 as a neutrophil chemoattractant in this disease. Bronchoalveolar lavage (BAL) fluid was harvested from calves experimentally infected with bovine herpesvirus-1 and challenged with Mannheimia haemolytica. Neutrophil chemotactic activity was measured in pneumonic BAL fluid samples treated with a neutralizing monoclonal antibody to ovine IL-8, and compared to the activity in samples treated with an isotype-matched control antibody. Bronchoalveolar lavage fluid was analyzed at a dilution which induced a half-maximal response, and the concentrations of antibody were optimized in a preliminary experiment. Following incubation of replicate samples of diluted pneumonic bovine BAL fluid with 70 microg/mL of IL-8-neutralizing antibody or control antibody, the neutrophil chemotactic activities of the samples were determined using an in vitro microchemotaxis assay. Overall, pretreatment of BAL fluid samples with neutralizing anti-IL-8 antibody reduced neutrophil chemotactic activity by 15% to 60%, compared to pretreatment with control antibody. This effect was highly significant (P < 0.001), and was present in 5 of 5 samples. These data indicate that IL-8 is an important neutrophil chemoattractant in calves with pneumonic pasteurellosis, but that mediators with actions redundant to those of IL-8 must also be present in the lesions.  相似文献   

4.
The interactions between leukocytes and cytokines during the acute response to intramammary infections in the dry mammary gland of sheep were studied. Dry ewes were experimentally infected in one udder half with either Staphylococcus aureus or Escherichia coli, or infused with saline as control. Udder secretion samples, blood samples and udder tissue samples were collected before and 4, 8 and 24 h after infections/infusions. Total and differential leukocyte counts were calculated in both blood and mammary secretions, and flow cytometry was used to detect the presence of CD4+, CD8+, WC1+, IL-2R+, CD18+ or L-selectin + lymphocytes, CD18+ or L-selectin + neutrophils, and CD14+ leukocytes. Moreover, the concentrations of interleukin-1 beta (IL-1 beta), interleukin-8 (IL-8) and granulocyte-macrophage colony stimulating factor (GM-CSF) in udder secretions were measured using ELISA, and RT-PCR was used to detect the presence of corresponding cytokine mRNA in udder tissue biopsies. The results suggest an association between the concentrations of IL-1 beta, IL-8 and the intensity of neutrophil infiltration of the infected gland. Immunologically relevant changes in proportions of lymphocyte subpopulations might also occur in the acute phase of the inflammatory reaction of the udder. Greater cellular and cytokine responses to E. coli infection may have contributed to the milder clinical picture and more rapid resolution of infection than that seen for S. aureus. Enhancing the production of pro-inflammatory cytokines may improve defence against bacterial mastitis.  相似文献   

5.
The interactions between leukocytes and cytokines during the acute response to intramammary infections in the dry mammary gland of sheep were studied. Dry ewes were experimentally infected in one udder half with either Staphylococcus aureus or Escherichta coli, or infused with saline as control. Udder secretion samples, blood samples and udder tissue samples were collected before and 4, 8 and 24 h after infections/infusions. Total and differential leukocyte counts were calculated in both blood and mammary secretions, and flow cytometry was used to detect the presence of CD4+, CD8+, WC1+, IL-2R+, CD18+ or L-selectin+ lymphocytes, CD18+ or L-selectin + neutrophils, and CD14+ leukocytes. Moreover, the concentrations of interleukin-1β+ (IL-1β), interleukin-8 (IL-8) and granulocyte-macrophage colony stimulating factor (GM-CSF) in udder secretions were measured using ELISA, and RT-PCR was used to detect the presence of corresponding cytokine mRNA in udder tissue biopsies. The results suggest an association between the concentrations of IL-1β, IL-8 and the intensity of neutrophil infiltration of the infected gland. Immunologically relevant changes in proportions of lymphocyte subpopulations might also occur in the acute phase of the inflammatory reaction of the udder. Greater cellular and cytokine responses to E. coli infection may have contributed to the milder clinical picture and more rapid resolution of infection than that seen for S. aureus. Enhancing the production of pro-inflammatory cytokines may improve defence against bacterial mastitis.  相似文献   

6.
Interleukin 8 (IL-8) is a potent chemotactic and activating agent for human neutrophils and bovine IL-8 is chemotactic for bovine neutrophils; however, it is unclear whether IL-8 activates bovine neutrophils. Two isoforms of human recombinant (hr) IL-8 protein (77 and 72 amino acid) were used to stimulate bovine neutrophils in vitro. Bovine neutrophils exhibited significant migration in the presence of 0.1, 0.5, 1.0 and 5.0ngml(-1) hr IL-8 when incubated for 30min at 37 degrees C in a modified Boyden chamber assay. Both the 77 and 72 aa forms were equally effective in inducing migration in this assay. At the highest doses of IL-8 examined (1 and 5ngml(-1)), migration was similar to migration in the presence of 20% zymosan-activated serum (ZAS) or 12h lipopolysaccharide (LPS)-stimulated blood monocyte supernatants (CM). Significant (p<0. 05) release of alkaline phosphatase (ALK-P) (from specific granules) occurred but myeloperoxidase (MPO) release and superoxide anion production were not enhanced in bovine neutrophils by either form of hrIL-8 at any of the doses tested. Significant (p<0.05) alkaline phosphatase release was observed in the presence of 10 and 100ngml(-1) for the 72 aa form of IL-8 and only at the higher dose for the 77 aa form of IL-8. The ZAS and CM significantly enhanced neutrophil degranulation of ALK-P and MPO as well as inducing superoxide anion production. These results suggest that IL-8 may play a role in both neutrophil recruitment and activation during bovine inflammatory processes.  相似文献   

7.
OBJECTIVE: To determine the capacity of inflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), platelet-activating factor (PAF), lipopolysaccharide (LPS), and leukotoxin to prime, activate, or alter deformability of adult bovine neutrophils. SAMPLE POPULATION: Blood collected from 5 healthy adult Holstein cows. PROCEDURE: Isolated neutrophils or whole blood was incubated with TNF-alpha, IL-8, PAF, LPS, or leukotoxin, and neutrophil chemiluminescence, degranulation, deformability, shape change, CD11b expression, and size distribution was measured. RESULTS: Incubation with TNF-alpha, IL-8, PAF, and LPS primed neutrophils for oxygen radical release but caused minimal oxygen radical release by themselves. None of the inflammatory mediators induced degranulation. Incubation with TNF-alpha and PAF resulted in a decrease in neutrophil deformability and induced shape change in neutrophils. Incubation with PAF consistently resulted in an increase in neutrophil size as measured by use of flow cytometry. Only IL-8 caused an increase in expression of CD11b by neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: Inflammatory mediators tested had minimal effects on neutrophil oxygen radical production or degranulation but did prime neutrophils for oxygen radical production. Incubation with PAF and TNF-alpha caused a decrease in neutrophil deformability and altered neutrophil shape and size. Results of our study indicate that PAF- and TNF-alpha-induced changes in neutrophil deformability and size may cause integrin- and selectin-independent trapping of neutrophils in the lungs of cattle with pneumonic pasteurellosis.  相似文献   

8.
Objective— To investigate neutrophil accumulation after ischemia and reperfusion (IR) in microvascular tissue flaps in horses.
Study Design— Randomized controlled experiment.
Sample Population— A total of 8 horses between 1 and 10 years of age, 4 of each sex.
Methods— Control and experimental myocutaneous island flaps based on the superficial branch of the deep circumflex iliac vessels were dissected on each horse. Atraumatic vascular clamps were applied to the pedicle of the experimental flap for 90 minutes and then removed to allow reperfusion. Based on the assumption that rapid infiltration of neutrophils into affected tissues is a hallmark of IR injury, radiolabeled autogenous leukocytes were used to indirectly quantify neutrophil accumulation in flap tissues. Labeled leukocytes were administered through a jugular catheter 30 minutes before flap reperfusion. Biopsies were collected from each flap over a 6 hour postischemia time period; in group 1 (  n = 4  ) from 0 to 6 hours postischemia, and in group 2 (  n = 4  ) from 24 to 30 hours postischemia. Biopsies were examined scintigraphically and histologically for evidence of neutrophil infiltration.
Results— All control flaps survived and 6 of 8 experimental flaps survived. There was no significant evidence of acute neutrophil infiltration into flap tissues after reperfusion in either group.
Conclusions— The results of this study suggest that equine myocutaneous flap tissues can survive a 90-minute ischemic period and reperfusion. No significant evidence of the occurrence of IR injury in flap tissues was found.
Clinical Relevance— The reasons for the previously reported failures of equine free tissue transfer remain uncertain, but they do not appear to be caused by neutrophil mediated injury associated with ischemia and reperfusion.  相似文献   

9.
The acute stages of infection with swine influenza virus (SIV), porcine respiratory coronavirus (PRCV) and porcine reproductive-respiratory syndrome virus (PRRSV) were shown to differ in terms of clinical and lung inflammatory effects and proinflammatory cytokine profiles in bronchoalveolar lavage (BAL) fluids. Caesarian-derived colostrum-deprived pigs were inoculated intratracheally with one of the three viruses. SIV infection was followed within 1 day post inoculation (d PI) by characteristic respiratory and general signs, and excessive lung epithelial desquamation and neutrophil infiltration (38 to 56 per cent of BAL cells at 1 d PI vs 0 to 1 per cent in controls). High concentrations of bioactive interferon-alpha (IFN -alpha), tumour necrosis factor-alpha (TNF -alpha) and interleukin-1 (IL -1) coincided with peak symptoms and neutrophil infiltration. PRCV infection was asymptomatic and produced a mild bronchointerstitial pneumonitis and neutrophil infiltration (13 to 22 per cent of BAL cells at 4 d PI). IFN -alpha titres parallelled those found during SIV infection, TNF -alpha was negligible and IL -1 undetectable. PRRSV infection induced anorexia and lethargy between 3 and 5 d PI. There was marked infiltration with mononuclear cells in alveolar septa and BAL fluids between 7 and 10 d PI, while neutrophils remained at less than 11 per cent of BAL cells at any time. IL -1 was produced from three throughout 10 d PI, while IFN -alpha production was minimal and TNF -alpha undetectable. These data strongly suggest that proinflammatory cytokines can be important mediators of viral respiratory disease.  相似文献   

10.
The effects of selenium (Se) supplementation and source on equine immune function have not been extensively studied. This study examined the effects of oral Se supplementation and Se source on aspects of innate and adaptive immunity in horses. Fifteen horses were assigned to 1 of 3 groups (5 horses/group): control, inorganic Se (sodium selenite), organic Se (Se yeast). Immune function tests performed included: lymphocyte proliferation in response to mitogen concanavalin A, neutrophil phagocytosis, antibody production after rabies vaccination, relative cytokine gene expression in stimulated lymphocytes [interferon gamma (IFNγ), interleukin (IL)-2, IL-5, IL-10, tumor necrosis factor alpha (TNFα)], and neutrophils (IL-1, IL-6, IL-8, IL-12, TNFα). Plasma, red blood cell Se, and blood glutathione peroxidase activity were measured. Plasma and red blood cell Se were highest in horses in the organic Se group, compared with that of inorganic Se or control groups. Organic Se supplementation increased the relative lymphocyte expression of IL-5, compared with inorganic Se or no Se. Selenium supplementation increased relative neutrophil expression of IL-1 and IL-8. Other measures of immune function were unaffected. Dietary Se content and source appear to influence immune function in horses, including alterations in lymphocyte expression of IL-5, and neutrophil expression of IL-1 and IL-8.  相似文献   

11.
Interleukin-8, a member of the chemokine family of cytokines, is a potent neutrophil chemoattractant in many non-rodent species. In this study, recombinant bovine interleukin-8 (rbIL-8) was expressed in bacteria as a glutathione-S-transferase fusion protein. The fusion protein was purified by glutathione-Sepharose affinity chromatography and recombinant rbIL-8 was eluted by cleaving with thrombin. The purified rbIL-8 molecule was approximately 8 kDa and was confirmed as authentic IL-8 by Western analysis. Recombinant bovine IL-8 induced specific dose-dependent in vitro chemotaxis of neutrophils at doses as low as 1.0 ng/ml, and this activity was inhibited by pre-treatment of rbIL-8 with a monoclonal antibody to ovine IL-8. Neutrophils exposed to rbIL-8 developed pseudopodia and became elongated as determined by microscopic analysis and flow cytometry. Injection of 3.3 ng to 3.3 microg of rbIL-8 into the skin of a normal calf induced dose-dependent recruitment of neutrophils but not eosinophils. Intravascular margination of neutrophils was obvious at the injection sites from 15 to 60 min after administration of rbIL-8, and extravascular neutrophil numbers increased steadily from 1 to 18 h after injection. Neutrophils with morphologic features of apoptosis were detected in these lesions at 18 and 30 h after injection, and this correlated with reduction in the number of dermal neutrophils. These results confirm unequivocally that bovine IL-8 functions as a neutrophil, but not an eosinophil, chemoattractant in vitro and in vivo.  相似文献   

12.
The phagocytic and killing abilities of heifer mammary gland macrophages (M phi) and neutrophils were evaluated after exposure to recombinant bovine interferon-gamma (rBoIFN-gamma) stimulation in vitro. Macrophages or neutrophils were cultured for 2 h with 0, 10(2), 10(4) and 10(5) units rBoIFN-gamma/mL. Phagocytosis assays were performed by incubation with Staphylococcus aureus at a leukocyte:bacteria ratio of 1:10. After 45 min, cells were stained with acridine-orange and phagocytic and killing abilities were determined. Although rBoIFN-gamma had no effect on M phi phagocytic activity, neutrophil phagocytic activity after incubation in 10(4) units rBoIFN-gamma (41.62%) was significantly higher than 0 (25.24%) or 10(2) units rBoIFN-gamma (24.73%). Neutrophil and M Phi killing abilities were not affected by any dose of rBoIFN-gamma. Results suggested that rBoIFN-gamma promoted neutrophil phagocytic activity, but did not affect neutrophil killing or overall M phi function in vitro.  相似文献   

13.
The administration with high dose (close to LD50) of thioacetamide (TAA), a hepatotoxicant used widely to induce experimental liver lesions, develops hepatocellular necrosis and subsequent inflammation (mainly M1-/M2-macrophages without neutrophil infiltration) in rats. We analyzed rat livers treated with a low dose TAA (50 mg/kg/body weight) at 6, 12, 18, 24 and 48 hr. The lesions in the affected centrilobular areas consisted of slight hepatocyte degeneration at 12 hr, and inflammatory cell infiltration at 18 and 24 hr; the lesions recovered until 48 hr. Translocation of intranuclei to cytoplasm of HMGB1, a representative molecule of damage-associated molecular patterns, was seen in some hepatocytes mainly at 6, 12, and 18 hr. As an interesting finding, at 12 hr, myeloperoxidase-positive neutrophil infiltration was observed in the affected centrilobular area. Additionally, CD68 M1-/CD163 M2-macrophages increased consistently at 12 to 48 hr. CXCL1, a chemokine for induction of neutrophils, began to increase at 6 hr and gradually increased at 12, 18 and 24 hr, apparently corresponding to the appearance of neutrophils. Collectively, the present findings at the low dose TAA indicated that along with M1-/M2-macrophages, neutrophils were characteristically seen, which might be elicited by cytoplasmic translocation of HMGB1 from nuclei. These finding would be useful for evaluation of hepatotoxicity at the early stages.  相似文献   

14.
Interleukin 17 (IL-17) mediates neutrophil migration to the lungs during acute inflammation, potentially leading to lung tissue damage. In the present study, we evaluated whether IL-17 could facilitate certain neutrophil functions in a mouse model. Mice were divided into four groups and intranasally challenged with PBS (1 = Control), Influenza A (H1N1) and Klebsiella pneumoniae (2 = Mix), Influenza A alone (3 = Flu), or K. pneumoniae (4 = KP) alone. Bone marrow, BAL cells, and lung specimens were collected seven days post-challenge for analysis. Mice in the Flu group showed the highest mortality rate. Neutrophils were the prominent cell type in BAL from Mix and KP, whereas lymphocytes were most numerous in Flu. Lesions in the lungs revealed considerably damage in the Mix, Flu, and KP groups. Isolated bone marrow-derived neutrophils were in vitro primed with mouse recombinant IL-17A protein (rIL-17A) followed by various functional assays. The reactive oxygen species (ROS) levels in rIL-17A primed cells showed significant elevations in all groups. Phagocytosis and bacterial destruction showed no significant difference between (+) or (−) rIL-17A groups. The formation of neutrophil extracellular traps (NETs) in rIL-17A-primed neutrophils showed elevated NET production. We next monitored expressions of genes in neutrophils. IL-17A mRNA expression was significantly increased in Mix and Flu; IL-1β mRNA only significantly increased in Flu, and IL-17RA showed constitutive expressions in all groups. In summary, neutrophils may cause tissue damage during lung inflammation through specific functions influenced by IL-17.  相似文献   

15.
Laminitis is known to involve deregulation of proteases and destruction of the lamellar basement membrane with the host inflammatory response also playing a role. Leukocyte infiltration has been well characterized in the black walnut model of laminitis induction, but not in carbohydrate induced models. Increased gene expression of multiple cytokines, including IL-6, has also been implicated in laminitis development. Using real time PCR, immunohistochemistry and zymography methods, we characterize leukocyte infiltration and IL-6 gene expression in oligofructose (OF) induced laminitis. As well, we use two in vitro models to investigate a role for IL-6 in protease regulation. Laminitis was induced in normal standardbred horses (n=5) by alimentary OF dosing and lamellar biopsies were obtained throughout the 48 h experimental period. Lamellar explants and keratinocytes were also isolated from clinically normal horses for in vitro experiments. We found infiltration of calprotectin-positive leukocytes (monocytes and neutrophils) at 18-24h post oligofructose dosing, while IL-6 gene expression was increased as early as 12h post dosing. Additionally, while we found that IL-6 did not cause significant BM damage in vitro, it did result in increased secreted proMMP-9 levels from lamellar explants. Thus, we find that leukocyte infiltration does occur during oligofructose-induced laminitis development, however, IL-6 gene expression in the lamellae may precede leukocyte infiltration. Additionally, we show IL-6 plays a role in increasing the level of proMMP-9 in vivo in a manner that does not involve keratinocytes.  相似文献   

16.
Adenovirus-mediated gene delivery of anticytokines is a powerful tool for modulating the cytokine environment under conditions of respiratory disease. In order to determine the feasibility of cytokine modulation in the context of respiratory disease in swine, nonreplicating E1- and E3-deficient adenovirus constructs expressing a model protein, beta-galactosidase, and an anticytokine, the IL-1 receptor antagonist (IL-1Ra), were evaluated for in vitro expression in porcine PK15 cells, and in vivo following endotracheal instillation into the lungs. beta-Galactosidase and IL-1Ra were readily expressed in vitro in swine cells. Endotracheal administration of lacZ-containing adenovirus demonstrated that endothelial and epithelial cells in the alveolar spaces and bronchi of the middle and lower lobes were the principal sites of infection and expression, whereas beta-galactosidase staining was not observed in the upper lobe. Endotracheal administration of IL-1Ra recombinant adenovirus resulted in sustained expression of IL-1Ra into the alveolar spaces, where it was recovered in a concentration of 660 pg/ml in 500 ml of lavage fluid, equivalent to 330 ng IL-1Ra, in the lungs 7 days after treatment. Moreover, in vivo instillation of nonreplicating adenovirus did not induce an inflammatory response in the 1-week time frame of the study period. Lung weight as a percent of body weight, serum zinc, serum amyloid A, leukocyte differentials, neutrophil activity, and TNF levels all were the same between untreated pigs and pigs treated with either recombinant adenovirus. The results indicate that the delivery of IL-1Ra to swine lungs via nonreplicating, recombinant adenovirus may be an effective method for in vivo modulation of IL-1 activity and investigation of cytokine involvement in respiratory disease pathogenesis.  相似文献   

17.
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18.
The degree to which the selectin inhibitor TBC1269 reduces neutrophil infiltration in specific microscopic locations of the lung during acute pneumonia of neonates was determined. Neonatal calves were inoculated intrabronchially with Mannheimia (Pasteurella) haemolytica or saline, and lung tissue was collected at 2 and 6 hours postinoculation (PI). One 6-hour group inoculated with M. haemolytica received TBC1269 intravenously before and after inoculation with M. haemolytica. Infiltrates of neutrophils were significantly higher in the alveolar lumen and septae but lower in the bronchial lumen and epithelium at 6 hours PI than at 2 hours PI. Significantly fewer neutrophils (P < 0.05) were present in the alveolar lumen and septae, and the bronchiolar lumen and lamina propria in the lungs of TBC1269-treated calves compared with untreated calves at 6 hours PI. TBC1269 did not alter the infiltration into bronchi and blood vessels or the expression of the selectin-independent adhesion molecule, ICAM-1. This work suggests that during acute pneumonia of neonates 1) neutrophil infiltrates progressively increase in the alveolar lumens and septae but decrease in the bronchial lumen and epithelium with time, 2) TBC1269 reduces neutrophil infiltration into specific regions of alveoli and bronchioles rather than uniformly throughout the lung, and 3) selectin inhibition does not affect the location and intensity of ICAM-1 expression.  相似文献   

19.
Inflammatory cytokines are suspected to contribute to the pathogenesis of bovine pneumonic pasteurellosis (BPP) through neutrophil recruitment, leukocyte activation, and the induction of a broad array of soluble inflammatory mediators. An in vivo experimental model of BPP was used to characterize the pulmonary expression kinetics of tumor necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta), and interleukin-8 (IL-8) genes and proteins during the acute phase of disease development. Cytokine expression in bronchoalveolar lavage (BAL) fluid, BAL cells, and pneumonic lung parenchyma was quantitated by northern blot analysis, enzyme-linked immunosorbent assay (ELISA), and in situ hybridization at 2, 4, 8, 16, and 24 hours after endobronchial inoculation of Pasteurella (Mannheimia) haemolytica. Expression of TNFalpha, IL-1beta, and IL-8 was significantly increased in the airways and lung lesions of infected calves as compared with mock-infected controls. Although kinetic patterns varied, peak levels of cytokine mRNA occured within 8 hours postinfection (PI), and peak cytokine concentrations occurred within 16 hours PI. In all samples, IL-8 was expressed to the greatest extent and TNFalpha was least expressed. Expression of TNFalpha was restricted to alveolar macrophages. Alveolar and interstitial macrophages produced IL-1beta and IL-8 in the first 4 hours; bronchial and bronchiolar epithelial cells were also significant sources of IL-8 during this period. By 8 hours PI, neutrophils were the dominant source of both IL-1beta and IL-8. These findings demonstrate a spatial and temporal association between pulmonary expression of inflammatory cytokines and acute lung pathology, supporting the hypothesis that cytokines contribute to inflammatory lung injury in BPP.  相似文献   

20.
The purpose of this study was to determine whether bovine thymocytes and fibroblasts preferentially respond to bovine IL-1 as compared with human and murine interleukin 1 (IL-1). We compared equivalents units of recombinant murine and human IL-1 alpha, and purified monocyte-derived bovine IL-1, as measured in the murine thymocyte IL-1 assay, for their ability to stimulate the proliferation of bovine thymocytes and fibroblasts. Fetal and adult bovine thymocytes responded to bovine IL-1, but in contrast, did not respond to recombinant human or murine IL-1 alpha at the concentrations tested. Both adult and neonatal murine thymocytes responded similarly to the three IL-1 preparations. Thus, we concluded that the preferential response of bovine thymocytes for bovine IL-1 was not dependent upon the age of the thymus donor. Bovine fibroblasts also preferentially responded to bovine IL-1; fibroblast proliferation was stimulated by bovine but not human or murine IL-1. Our findings, therefore, imply that although IL-1 is highly conserved among mammalian species, its ability to stimulate the proliferation of thymocytes and fibroblasts may vary from species to species.  相似文献   

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