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101.
Hagood JS Prabhakaran P Kumbla P Salazar L MacEwen MW Barker TH Ortiz LA Schoeb T Siegal GP Alexander CB Pardo A Selman M 《The American journal of pathology》2005,167(2):365-379
Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis. 相似文献
102.
103.
Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth. 总被引:2,自引:2,他引:2 下载免费PDF全文
We have previously shown that intranasal infection of mice with mouse hepatitis virus (MHV) strain UAB (MHV-UAB) increases their resistance to Salmonella typhimurium injected intravenously 6 days later. To study how salmonella resistance was induced, BALB/cAnNCr mice were infected with salmonella strains carrying specific genetic alterations. One set of studies compared the effect of MHV infection on subsequent salmonella infections with AroA- (avirulent) and Aro+ (virulent) salmonellae. Unlike its effect on Aro+ salmonellae, MHV failed to reduce the number of AroA- salmonellae recovered from mice. Because AroA- S. typhimurium shows almost no growth in vivo, this failure indicated that the effect of MHV on salmonella resistance required growth of the infecting salmonellae. In other studies, the effect of MHV infection on both growth and killing were monitored simultaneously in mice with growing salmonellae carrying a single copy of the temperature-sensitive pHSG422 plasmid, which is unable to replicate in vivo. MHV infection reduced salmonella growth but caused no increase in salmonella killing. MHV infection of mice given wild-type salmonellae also resulted in no increase in salmonella killing 4 h after salmonella challenge. These studies demonstrate that MHV-UAB infection increases host resistance to salmonellae by enhancing suppression of bacterial growth instead of by increasing the amount of salmonella killing. 相似文献
104.
D. Doyle C. J. Ryan I. S. Benjamin L. H. Blumgart 《International journal of experimental pathology》1978,59(5):461-466
Structural abnormalities are found in the astrocytes of the dentate nuclei of animals after portacaval shunting (PCS). These changes are also found in man in association with portal-systemic encephalopathy. To investigate the relationship between portal-systemic shunting and hepatocellular dysfunction in the pathogenesis of these changes, PCS and protacaval transposition (PCT) were performed in rats. PCT diverts portal blood into the systemic circulation, but retains normal total hepatic blood flow by perfusion with systemic venous blood. Liver function and mass are better preserved than after PCS. Abnormal glial cells were found in 4.03% of animals following sham operation, 13.45% following PCT, and 19.09% following PCS. Both experimental groups differed significantly from control animals, and the number of abnormal cells was significantly higher after PCS than after PCT. These findings are in keeping with the hypothesis that hepatocellular dysfunction plays an important role in addition to portal-systemic shunting in the aetiology of the structural changes in the brain associated with hepatic encephalopathy. 相似文献
105.
Mycobacterium-induced potentiation of type 1 immune responses and protection against malaria are host specific 总被引:2,自引:0,他引:2 下载免费PDF全文
Page KR Jedlicka AE Fakheri B Noland GS Kesavan AK Scott AL Kumar N Manabe YC 《Infection and immunity》2005,73(12):8369-8380
Malaria and tuberculosis are endemic in many regions of the world, and coinfection with the two pathogens is common. In this study, we examined the effects of long- and short-term infection with Mycobacterium tuberculosis on the course of a lethal form of murine malaria in resistant (C57BL/6) and susceptible (BALB/c) mice. C57BL/6 mice coinfected with M. tuberculosis CDC1551 and Plasmodium yoelii 17XL had a lower peak parasitemia and increased survival compared to mice infected with P. yoelii 17XL alone. Splenic microarray analysis demonstrated potentiation of type 1 immune responses in coinfected C57BL/6 mice, which was especially prominent 5 days after infection with P. yoelii 17XL. Splenocytes from coinfected C57BL/6 mice produced higher levels of gamma interferon (IFN-gamma) and tumor necrosis factor alpha than splenocytes from mice infected with either pathogen alone. Interestingly, mycobacterium-induced protection against lethal P. yoelii is mouse strain specific. BALB/c mice were significantly more susceptible than C57BL/6 mice to infection with P. yoelii 17XL and were not protected against lethal malaria by coinfection with M. tuberculosis. In addition, M. tuberculosis did not augment IFN-gamma responses in BALB/c mice subsequently infected with P. yoelii 17XL. These data indicate that M. tuberculosis-induced potentiation of type 1 immune responses is associated with protection against lethal murine malaria. 相似文献
106.
Differential cytokine induction by doses of lipopolysaccharide and monophosphoryl lipid A that result in equivalent early endotoxin tolerance. 总被引:3,自引:13,他引:3 下载免费PDF全文
The phenomenon of early endotoxin tolerance, which is induced by sublethal injection of lipopolysaccharide (LPS), results in a protracted period of hyporesponsiveness that is most profound at 3 to 4 days after injection and is marked by reduced cytokine production after a challenge injection of LPS. Early endotoxin tolerance is also induced by the nontoxic LPS derivative monophosphoryl lipid A (MPL), although much more of the monophosphoryl derivative is required to produce a state of tolerance equivalent to that evoked by LPS. In this study, equivalent tolerance-inducing doses of LPS and MPL were tested, and the levels of cytokines induced by LPS and MPL were compared. Although induced levels of colony-stimulating factor were comparable following doses of LPS and MPL that elicited an equivalent state of early endotoxin tolerance, levels of tumor necrosis factor, interleukin-6, and interferon were significantly lower in MPL-injected animals. These results suggest that the lowered toxicity of MPL may be related to its elicitation of significantly lower levels of potentially toxic intermediaries such as tumor necrosis factor, interferon, and interleukin-6. 相似文献
107.
The morphologic changes in lymphoreticular tissues and development of antitumor immune reactions of specific pathogen-free mice injected with syngeneic lymphoma cells were sequentially analyzed. The regional (right inguinal) lymph node demonstrated mild changes indicative of immunologic response. Systemic lymph nodes revealed a moderate degree of immune response on morphologic basis. The spleen was the site of marked activity, characterized by the presence of large pyroninophilic cells and germinal centers. Foci of necrosis in the local tumor accompanied by mature lymphocytes suggested cell-mediated immune rejection. Mice developed circulating antibodies 2 days after implantation. No antibodies were demonstrated attached to fresh tumor cells. Lymphocyte cytotoxic activity was demonstrated beginning on day 4. Both cytotoxic activity and circulating antibodies were no longer detectable after the third week following tumor implantation. Tumor-bearing mice also had an impaired capacity to mount a primary immune reaction to sheep red blood cells. The spleen demonstrated a marked loss of lymphocytes and the subsequent appearance of masses of amyloid material. It is suggested that amyloidosis in lymphoreticular organs is the result of a derangement in the immune response of the host following a prolonged and sustained antigenic stimulation. It appears that in syngeneic pathogen-free mice the spleen plays the major role in immune rejection mechanisms while the draining node only plays a modest role. 相似文献
108.
Fuller JR Pitzer JE Godwin U Albertino M Machon BD Kearse KP McConnell TJ 《Developmental and comparative immunology》2004,28(6):603-617
Folding and assembly of MHC molecules in mammals occurs in the endoplasmic reticulum (ER), but has not been studied in teleosts. Calnexin (CNX) is an ER chaperone that associates with glycoproteins bearing a monoglucosylated N-linked oligosaccharide side chain. Here we report the first identification and characterization of a full-length CNX cDNA clone in a teleost, and the association of the CNX chaperone with MHC class II in a channel catfish T cell line. The 1.8 kb CNX clone encodes a protein of 607 amino acids that is 72% identical to the consensus sequence of mammalian CNXs. The association of CNX with class II is of particular interest because the native MHC class II alpha chain of Ictalurus punctatus does not bear any N-linked oligosaccharide consensus glycosylation sequences. Thus the assembly of class II molecules in the catfish probably proceeds via different steps than occurs in mammals. 相似文献
109.
110.
Yeo GS Lank EJ Farooqi IS Keogh J Challis BG O'Rahilly S 《Human molecular genetics》2003,12(5):561-574
Mutations in the melanocortin-4 receptor gene (MC4R) represent the commonest monogenic cause of human obesity. However, information regarding the precise effects of such mutations on receptor function is very limited. We examined the functional properties of 12 different mutations in human MC4R that result in severe, familial, early-onset obesity. Of the nine missense mutants studied, four were completely unable to generate cAMP in response to ligand and five were partially impaired. Four showed evidence of impaired cell surface expression and six of reduced binding affinity for ligand. One mutation in the C-terminal tail, I316S, showed reduced affinity for alpha-MSH but retained normal affinity for the antagonist AgRP. None of the mutations inhibited signaling through co-transfected wild-type receptors. Thus, in the most comprehensive study to date of the functional properties of naturally occurring MC4R mutations we have (1) established that defective expression on the cell surface is a common mechanism impairing receptor function, (2) identified mutations which specifically affect ligand binding affinity thus aiding the definition of receptor structure-function relationships, (3) provided evidence against the notion that these receptor mutants act as dominant-negatives, and (4) identified a potentially novel molecular mechanism of receptor dysfunction whereby a mutation alters the relative affinities of a receptor for its natural agonist versus antagonist. 相似文献