ISSN:0741-5400    

DOI:10.1002/jlb.51.1.1

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

AbstractDecreased immune responses have been observed in hyperbilirubinemic patients. This study investigates bilirubin transport into human peripheral blood mononuclear cells (PBMNCs). In vitro incubation of PBMNCs at 37° with 0–12 mg/dl bilirubin in solution with a fixed bovine serum albumin (BSA) concentration (3.0 g/dl) resulted in a dose‐dependent increase of intracellular bilirubin in both monocytes and lymphocytes. Bilirubin uptake in monocytes was significantly higher (up to 2.7 times) than in lymphocytes under the same culture conditions. When PBMNCs were incubated with varying concentrations of bilirubin (0–16 mg/dl) in fixed BSA (3.0 g/dl) solution or at a fixed bilirubin/albumin molar ratio (0.4), the initial velocity of uptake in both cell fractions was proportional to the free (unbound to albumin) bilirubin concentration rather than the total bilirubin concentration. Bilirubin uptake by both cell fractions was significantly inhibited by treatment with metabolic inhibitors. Bilirubin uptake by monocytes continued to increase in parallel with incubation temperature from 0° to 40°, whereas uptake by lymphocytes reached a maximal level at 20° and remained constant thereafter. These results suggest that monocytes and lymphocytes incorporate bilirubin in proportion to the free bilirubin concentration and this function may rely on different energy‐dependent mechanisms.

ISSN:0741-5400    

DOI:10.1002/jlb.51.1.2

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

AbstractMouse T cell clones against liveMycobacterium aviumwere generated from the spleens of BALB/c mice infected withM. aviumTMC 702. Eighth clones were of the L3T4+subset, whereas two were of Lyt2+subset. Six of the L3T4+T cell clones were of the TH1subset whereas two were of the TH2subset, judged on the profile of cytokine release. One of the Lyt2+clones exhibited significant cytotoxicity againstM. avium‐infected mouse macrophages. Transfer of clones to nude BALB/c mice infected withM. aviumwas associated with insignificant changes in resistance for seven clones. One clone, of the L3T4+/TH2subset, transferred significant resistance to the infection, also associated with infusion of supernatants from the clone, which was fully inhibited by neutralizing with anti–interleukin 4. By contrast, infusion of one TH1clone and the cytolytic Lyt2+led to increased microbial growth in the spleens and livers of infected mice, which was not apparent on infusion with supernatants. Application of clones' supernatants on infected macrophages had marginal effects onM. aviumgrowth and was not correlated with protective or suppressive activity. Overall, these results suggest that T cells may influenceM.aviumgrowth in vivo in a bidirectional manner and also suggest that interleukin 4 may be an important factor in host resistance toM. avium.

ISSN:0741-5400    

DOI:10.1002/jlb.51.1.7

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

AbstractC‐reactive protein (CRP) is a prototypical acute‐phase reactant, the humoral and plasma concentrations of which rise dramatically after tissue injury or inflammation. The effects of CRP on superoxide production and intracellular calcium mobilization by guinea pig alveolar macrophages challenged with platelet‐activating factor (PAF),N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP), and phorbol 12‐myristate 13‐acetate (PMA) were studied. CRP by itself did not activate alveolar macrophages up to a concentration of 100 μg/ml, whereas it inhibited superoxide production in a time‐ and dose‐dependent manner with median inhibitory concentration (IC50) values of 4.2 ± 0.3,3.0 ± 0.2, and 3.2 ± 0.3 μg/ml for PAF (10‐7M), fMLP (10‐7M), and PMA (10‐9M), respectively. When CRP was incubated with the agonists before addition to cells, it inhibited PMA‐, PAF‐, and to a lesser extent fMLP‐induced superoxide production. CRP also attenuated the rise in intracellular free calcium levels evoked by fMLP or PAF in a dose‐dependent manner. These findings suggest that CRP may play a role in attenuating tissue damage secondary to activation of alveolar macrophages by inhibiting superoxide generation and mobilization of intracellular free calcium.

ISSN:0741-5400    

DOI:10.1002/jlb.51.1.13

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

AbstractNeutrophil‐induced alterations in feline erythrocytes were studied to better understand the pathogenesis of erythrocyte destruction associated with inflammatory diseases. As in previous studies, addition of superoxide dismutase/catalase to a coculture of erythrocytes and activated neutrophils attenuated neutrophil‐induced immunoglobulin G (IgG) binding. However, incubation of erythrocytes with hydrogen peroxide or neutrophil‐derived anuclear cytoplasts (neutroplasts) failed to induce IgG binding. Addition of phenylmethylsulfonyl fluoride, a serine protease inhibitor, to the erythrocyte‐neutrophil coculture attenuated IgG binding. These observations suggest that neutrophil‐derived serine protease activity is involved in IgG binding to erythrocytes. Further, incubation of erythrocytes with serine proteases, but not metalloproteases or sulfhydryl proteases, induced immunoglobulin binding. Freeze‐fracture replicas of the erythrocyte membrane failed to demonstrate clustering of band 3 protein, suggesting that spatial rearrangement of band 3 protein was not the cause of the IgG binding. Neutrophil‐induced IgG binding due to the combined action of proteases and oxidants may explain the accelerated destruction of erythrocytes in inflammatory diseases.

ISSN:0741-5400    

DOI:10.1002/jlb.51.1.19

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

AbstractMurine peritoneal macrophages (Møs), induced with stimuli such as thioglycollate, zymosan A, OK‐432, bacille Calmette‐Guérin (BCG), or liveMycobacterium intracellulare, showed varying levels of inhibitory activity against the concanavalin A (Con A) blastogenic response of splenic T cells. All test Møs significantly inhibited the interleukin 2 (IL‐2)–producing ability of T cells but this inhibition was not enough to explain the observed reduction in T cell Con A mitogenesis. In contrast, they markedly inhibited IL‐2–reactive T cell generation, and the inhibition was sufficient to cause the reduction in T cell mitogenesis. A general relationship was observed between immunosuppressive activity of a given Mø and its active oxygen‐producing ability (measured in terms of chemiluminescence) in response to phorbol myristate acetate triggering (r= .84,P<.005). However, the suppressor activity of test Møs was not reduced by superoxide dismutase and catalase, indicating that active oxygen radicals themselves did not mediate the expression of the immunosuppressive activity of these Møs. On the other hand, indomethacin (an inhibitor of prostaglandin synthesis) caused a partial reduction in their immunosuppressive activity. The suppressor activity of Møs induced with intraperitoneal injection of recombinant interferon γ (IFN‐γ) was markedly reduced in the presence of myoglobin, a scavenger for nitric oxide radical (NO·). Tumor necrosis factor α (TNF α) failed to affect Con A mitogenesis of splenic T cells, even in combination with IFN‐γ. On the other hand, unsaturated long‐chain fatty acids including oleic, linoleic, linolenic, and arachidonic acids markedly reduced the T cell function. These findings suggest some important roles of prostaglandins, NO·, and long‐chain unsaturated fatty acids as mediators of the expression of immunosuppressive function of the peritoneal Møs.

ISSN:0741-5400    

DOI:10.1002/jlb.51.1.24

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

AbstractAn interleukin 3 (IL‐3)–dependent macrophage‐like cell line, 11‐1‐B3, was newly established from CBA/J mouse bone marrow cell cultures. Assay of eicosanoids in the culture supernatants of the intact and [3H]arachidonic acid (AA)–prelabeled cells showed that, after stimulation with the Ca2+ionophore A23187, the 11‐1‐B3 cells synthesized and released relatively large amounts of prostaglandin E2(PGE2) and leukotriene B4(LTB4) but not LTC4. In addition, 11‐1‐B3 cells showed Ca2+‐dependent and alkaline pH–optimal phospholipase A2(PLA2) activity that preferentially hydrolyzed cleavage ofsn‐2‐arachidonyl‐ but notsn‐2‐oleoylphosphatidylcholine. The cellular enzyme was distributed with 90% of the activity in the cytosol and 10% in the membrane fraction. Treatment of cells with A23187 for 5–10 min resulted in five‐ to sevenfold increases in the membrane‐associated PLA2but activity in the cytosol was unchanged. This increase in membrane‐associated enzyme activity was transient, returning to the pretreatment distribution after 30 min. In sharp contrast, phorbol myristate acetate (PMA) stimulation failed to induce either eicosanoid release or PLA2activation, although PMA induced translocation of protein kinase C (PKC) to the membrane fraction within 10 min. The data suggest that increases in cellular Ca2+directly activate membrane‐associated PLA2and consequently initiate AA metabolism; PKC activation by PMA requires additional steps to activate PLA2, a mechanism that is apparently deficient in the IL‐3–dependent Mø‐like cells.

ISSN:0741-5400    

DOI:10.1002/jlb.51.1.32

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

AbstractActivation of liver macrophages during clearance of endotoxins, bacteria, or other particulate materials may be accompanied by the migration of polymorphonuclear neutrophils (PMNs) into the liver and priming of the hepatic phagocytes to release toxic oxygen metabolites. In the present study we investigated the effect of in vivo administration of latex particles on the hepatic sequestration of PMNs and the release of superoxide anion (O2‐) by the in situ perfused rat liver and isolated hepatic phagocytes. One hour after an intravenous injection of latex beads, a significant amount of O2‐(0.7 nmol/min/g) was produced by the in situ perfused liver. Administration of latex particles into the perfused liver also elicited O2‐production. Hepatic phagocytes from latex‐treated rats generated large amounts of O2‐(2–14 nmol/60 min/106cells) when these cells were stimulated in vitro with opsonized zymosan or phorbol myristate acetate (PMA), whereas phagocytes from saline‐treated rats released less than 0.8 nmol O2‐. Intravenous infusion of superoxide dismutase or ibuprofen did not prevent the immigration of PMNs to the liver. However, ibuprofen inhibited the production of O2‐by the perfused liver. Also, after addition of ibuprofen in vitro to isolated cells, there was more than 50% inhibition of O2‐generation by Kupffer cells and hepatic PMNs treated with either zymosan or PMA. These observations suggest that arachidonic acid metabolites play a role in O2‐release under these conditions. Thus, activation of the reticuloendothelial system by latex phagocytosis induces the migration of PMNs into the liver and enhances the production of toxic oxygen‐derived radicals by these cells and the resident Kupffer cells. The toxic oxygen radicals may also contribute to hepatic injury.

ISSN:0741-5400    

DOI:10.1002/jlb.51.1.39

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

AbstractThe influence of aging on neutrophil chemotaxis, chemokinesis, and superoxide production was investigated in rats. Animals of two age groups, 3 to 4 months and 20 to 21 months, were used. Equivalent neutrophil chemotactic responses toN‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP), leukotriene B4(LTB4), and bacterial lipopolysaccharide (LPS)‐activated plasma were observed in both groups of animals, with cells suspended in Hanks' balanced salt solution (HBSS). However, cross‐incubation studies in which cells from young adult rats were exposed to plasma from aged donors, then resuspended in HBSS for testing, showed marked changes in the ability of the cells to respond to the chemoattractants. The response to LPS‐activated plasma was reduced, whereas responses to fMLP and LTB4remained unaltered. Previous incubation of the cells with homologous plasma from young donors produced no effect. The inhibitory activity developing with advancing age affected not only chemotaxis but also random movement stimulated by LPS‐activated plasma. The inhibitory activity of chemotaxis and chemokinesis in plasma of aged animals was heat labile (56°), vanished in the presence of a proteolytic enzyme like trypsin, and was maintained after dialysis with 12,000‐Mrretention dialysis tubing. The material did not influence superoxide production by stimulated neutrophils. It is suggested that inhibition of neutrophil locomotion with advancing age is associated with a plasma protein capable of interacting with neutrophil receptors for complement‐derived chemoattractants. The inhibitory substance might influence neutrophil responses to infection and inflammation in the elderly.

ISSN:0741-5400    

DOI:10.1002/jlb.51.1.46

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

AbstractRecombinant human interleukin 1 (IL‐1) administered as a “priming” agent 24 h prior to hematopoietically lethal doses of total body irradiation (TBI) confers radioprotection to normal G57B1/6 (B6) mice, but not to B6 tumor‐bearing animals (TBAs) known to have altered hematopoietic steady states. Using the Lewis lung tumor (LLca) in the B6 mouse, studies were carried out to determine whether the failure of IL‐1 to radioprotect the LLca TBA was related to a preexisting “primed” hematopoietic state in the TBA or resulted from inhibition of myelopoietic activity associated with the production of prostaglandin E (PGE) by, or in response to, the tumor. Both normal B6 and LLca B6 TBAs were injected (every 24 h × 1–5) with 100 μg of indomethacin (IND) prior to the administration of IL‐1. A single treatment with IND was sufficient to reduce the elevated levels of PGE found in the plasma of the TBAs. After five treatments, IND reduced the PGE level to below that of controls. Neither the acute nor the protracted IND treatment, however, affected the expansion of the stem and progenitor cell compartments of the marrow in the LLca TBA. Furthermore, no evidence of restoration of the radioprotective properties of IL‐1 was observed in TBAs pretreated with IND. Collectively, these data suggest that the failure of IL‐1 to provide radioprotection to the LLca TBA is not a direct result of the elevated plasma PGE levels associated with growth of the LLca tumor. In addition, these studies provide insight into the importance of examining in vivo effects of biological molecules in altered, as well as normal, physiological states.

ISSN:0741-5400    

DOI:10.1002/jlb.51.1.53

出版商:Wiley    

年代:1992

数据来源: WILEY