摘要:

AbstractSome T cells release proteins that bind specifically to antigens that have not been processed by antigen‐presenting cells. These soluble immunoproteins induce or effect antigen‐specific T cell functions in immunoregulation and/or hypersensitivity. After certain immunization regimens, T cell immunoproteins specific for the immunogen rise in serum, and therefore may be an antigen‐specific, humoral manifestation of the activation of some T cells during an immune response. Although non‐MHC (major histocompatibility complex)‐associated antigen is bound, soluble antigen‐specific T cell immunoproteins share variable and constant region epitopes and some amino acid sequence with the T cell receptor for antigen α or β chains, and their expression depends on T cell receptor structural genes. Herein, the properties of extracellular antigen‐specific T cell immunoproteins are reviewed and it is suggested that these molecules are a soluble analogue of the T cell receptor for antigen and provide an amplifying element for some T cell functions.

ISSN:0741-5400    

DOI:10.1002/jlb.59.5.605

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractThe ability of macrophages and neutrophils to defend tissue homeostasis and participate in inflammatory responses depends on their ability to mobilize granule‐membrane proteins and granule content into their external milieu and into phagosomes by regulated secretory processes. Many laboratories have invested much time and effort into furthering our understanding of vesicular transport and secretion. A surge of interest in phagocytosis and phagosomal maturation is also apparent (e.g., the March 1995 issue ofTrends in Cell Biologywas entirely devoted to phagocytosis). The signaling and the regulation of the secretory response are most likely different for secretion into phagosomes than for secretion into the external milieu. However, these differentially targeted secretory processes rely both upon proteins in vesicular membranes, plasma membrane/phagosomal membrane, and cytosol and upon their interactions with cytoskeletal structures. It is the complex molecular interactions between these components that form the basis for regulation and control of secretion. In the following, the signaling role of granular and cytosolic pH in phagocyte lysosomal secretion is discussed and the current literature on regulated secretion by macrophages and neutrophils is reviewed.

ISSN:0741-5400    

DOI:10.1002/jlb.59.5.613

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractSevere burn injury is associated with increased susceptibility to severe herpesvirus infections. Type 2 cytokines [interleukin (IL)‐4 and IL‐10] released from burn‐associated CD8+type 2 T cells (BA‐type 2 T cells) have been shown to play a role in the increased susceptibility of thermally injured mice (TI‐mice) to herpes simplex virus type 1 (HSV‐1) infection. Because IL‐12 has been shown to inhibit the generation of type 2 T cells, murine rIL‐12 was injected into TI‐mice exposed to HSV‐1 to determine whether IL‐12 could influence HSV‐1 infections in individuals bearing type 2 T cells. rIL‐12 improved the resistance of TI‐mice or mice inoculated with T6S cells (a BA‐type 2 T cell clone) against HSV‐1 infection. Type 2 cytokines were detected in sera of TI‐mice or mice inoculated with T6S cells (T6S‐mice). However, treatment of TI‐mice or T6S‐mice with rIL‐12 inhibited type 2 cytokine production in the sera of these mice. All TI‐mice exposed to a lethal dose of HSV‐1 survived when they were treated with a mixture of monoclonal antibodies (mAbs) against type 2 cytokines. Staphylococcal enterotoxin A [an interferon‐γ (IFN‐γ) inducer] stimulated serum IFN‐γ production in TI‐mice and T6S‐mice treated with rIL‐12, whereas no IFN‐γ was produced in mice treated with saline. These results suggest that IL‐12 has the potential to protect TI‐mice infected with a lethal dose of HSV‐1 via a shift to type 1 T cell responses from type 2 T cell responses.

ISSN:0741-5400    

DOI:10.1002/jlb.59.5.623

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractTo study neutrophil circulation time and trafficking in vivo requires labeling the cells so that their movement can be followed temporally and spatially. Labeling procedures used to date, however, have relied on ex vivo separation and labeling methods, an undesired consequence of which may be neutrophil activation. Moreover, the labeled cells preferentially stick in the pulmonary circulation for several hours upon reinjection into the host. Therefore, we devised an alternate labeling procedure that relied on intra‐arterial infusion of the fluorescent phagocytic cell linker PKH26. We infused PKH26 (5.5 × 10‐6M for 1 h) into six awake sheep and measured systemic and pulmonary hemodynamics and lung lymph dynamics continuously for 3–4 h after the infusion. We collected simultaneous arterial and venous blood samples hourly for 4 h, and again 24 h after the infusion ended, for white blood cell and neutrophil differential counts and to identify labeled cells in fresh smears by fluorescence and differential interference contrast (DIC) microscopy. Infusion of PKH26 had minimal and transient physiologic effects on systemic and pulmonary artery pressure, lung lymph flow, and leukocyte counts. Labeled cells were present in venous blood after the infusion for at least 24 h. DIC microscopy observation of the blood smears indicated that the fluorescently labeled cells were exclusively neutrophils. Unstimulated superoxide anion release from neutrophils isolated 2 and 24 h after PKH26 infusion was not different from baseline release. Phorbol myristate acetate‐stimulated release was not affected either. The labeled neutrophils responded to chemoattractants by migrating to extravascular sites. Our results indicate that neutrophils can be selectively labeled in vivo, after which trafficking of the labeled neutrophils can be determined.

ISSN:0741-5400    

DOI:10.1002/jlb.59.5.631

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractGlucose is the primary metabolic substrate of macrophages, which are critical components of the host response to injury and infection. We have carried out a series of studies to examine macrophage glucose uptake and the status of glucose transporter 1 (GLUTI) at both the mRNA and protein level. Peritoneal macrophages that were obtained from mice undergoing sham burned (S), 15%TBSA burn (B)±Pseudomonas aeruginosaburn infection (B + I) and lipopolysaccharide (LPS) or tumor necrosis factor‐α (TNF‐α) administration. [3H]deoxyglucose uptake was significantly increased (B, 157 ± 9%; B + I, 243 ± 19%; S + LPS, 231 ± 24%; S + TNF‐α, 379 ± 18%; B + LPS, 230 ± 13%; and B + TNF, 305 ± 23%,P<0.01 vs. sham). GLUTI mRNA and protein levels were increased as well (mRNA: B, 135 ± 13%; B + I, 250 ± 33%; S + LPS, 282 ± 29%; S + TNF‐α, 193 ± 19%; B + LPS, 378 ± 20%; and B + TNF‐α, 204 ± 16%; protein: B, 159 ± 27%; B + I, 181 ± 17%; S + LPS, 219 ± 26%; S + TNF‐α, 343 ± 51%; B + LPS, 366 ± 41%; and B + TNF‐α, 415 ± 44,P<0.01 vs. sham). Macrophages co‐cultured with LPS or TNF‐α in vitro demonstrated a similar response pattern. Following burn injury and infection, macrophages augment their cellular glucose uptake, which is facilitated by an increased GLUT1 mRNA and protein levels. TNF‐α elicited by LPS may mediate this enhanced carbohydrate metabolism at the point of glucose entry into the cell.

ISSN:0741-5400    

DOI:10.1002/jlb.59.5.639

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractBoth human integrin receptors Mac‐1 (CD11b/CD18, CR3) and lymphocyte function‐associated antigen (LFA)‐1 (CD11a/CD18) have been demonstrated to bind human intercellular adhesion molecule‐1 (ICAM‐1) (CD54). Here we show that LFA‐1 and Mac‐1 can bind to ICAM‐1 in the mouse as well. Interestingly, we observed that binding of murine LFA‐1 dominates over Mac‐1 for binding to ICAM‐1. Using three different murine macrophage cell lines that express distinct levels of LFA‐1 and Mac‐1 on their cell surface, we could only detect Mac‐1‐dependent adhesion to ICAM‐1 when little or no LFA‐1 is expressed on the cell surface. When LFA‐1 and Mac‐1 are expressed at similar levels, the LFA‐1/ICAM‐1 interaction dominates over Mac‐1/ICAM‐l interaction, indicating that there is a competition of LFA‐1 and Mac‐1 for ICAM‐1 binding.

ISSN:0741-5400    

DOI:10.1002/jlb.59.5.648

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractT cell‐mediated immunity againstChlamydiain mice is mediated at least in part by T cell‐derived interferon‐γ (IFN‐γ) induction of the nitric oxide synthase (iNOS) system in infected epithelial cells. Although IFN‐γ alone could stimulate nitric oxide (NO) production from epithelial cells and inhibit the intracellular growth ofChlamydia, the effectiveness was less than when infected epithelial cells were co‐cultured with IFN‐γ‐producing T cell clones. In co‐cultures containing T cells and infected epithelial cells, additional NO produced by activated T cells could augment chlamydial killing; however, T cell‐derived NO was insufficient to account for the total NO present in the co‐culture and therefore could not explain the dramatic increase in chlamydial inhibition under those conditions. To determine whether direct cell‐to‐cell interaction involving adhesion molecules was involved in increased NO induction, the ability of neutralizing monoclonal antibodies directed against intercellular adhesion molecule type 1 (ICAM‐1) and leukocyte function antigen‐1 (LFA‐1) to suppress NO production and lower intracellular chlamydial inhibition was investigated. It was found that monoclonal antibodies against ICAM‐1/LFA‐1 could significantly reduce the capacity of a protective CD4+ type 1 (Th1) clone (clone 2.14‐0) to inhibit the intracellular growth of theC. trachomatisagent of mouse pneumonitis (MoPn). The suppression of the anti‐chlamydial action of the clone by antibodies correlated with ~50% decrease in NO production. Also, paraformaldehyde‐fixed clone 2.14‐0 could enhance NO induction and chlamydial inhibition mediated by IFN‐γ, and this effect could be reversed by anti‐ICAM‐1/LFA‐1 antibodies. The results indicated that epithelial‐T cell interaction via adhesion molecules enhances NO production and increased chlamydial inhibition by IFN‐γ‐secreting T cells.

ISSN:0741-5400    

DOI:10.1002/jlb.59.5.656

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractNeutrophil stimulation results in the activation of a variety of phospholipases, including phospholipase A2(PLA2), which releases arachidonic acid from the 2 position of membrane phospholipids, leaving a lysophospholipid. Because arachidonic acid is known to be a potent fusogen in vitro, we examined the effect of metabolism by PLA2on the fusion of complex liposomes (liposomes prepared with a phospholipid composition similar to that found in neutrophil plasma membrane). We observed that PLA2augmented the fusion of complex liposomes with each other as well as with specific granules isolated from human neutrophils, lowering the Ca2+requirement for fusion by three orders of magnitude. Furthermore, although lysophospholipids inhibited fusion, the incorporation of arachidonic acid into liposome membranes overcame the inhibitory effects of the lysophospholipids. Thus with PLA2 and annexins we were able to obtain fusion of complex liposomes at concentations of Ca2+that are close to physiological. Our data suggest that the activation of PLA2and the generation of arachidonic acid may be the major fusion‐promoting event mediating neutrophil degranulation.

ISSN:0741-5400    

DOI:10.1002/jlb.59.5.663

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractAdenosine has been shown to inhibit the adhesion of polymorphonuclear leukocytes (PMNL) to the vascular endothelium. Because the underlying molecular mechanisms have not been fully understood, the present study characterizes the effect of adenosine on the expression of adhesion molecules of human PMNL. When PMNL were activated byN‐formyl‐methionyl‐leucyl‐phenylalanine the number of cell surface β2integrins increased fivefold, whereas L‐selectin molecules were completely shed. Activation‐dependent numerical up‐regulation of β2integrins and shedding of L‐selectin were inhibited by exogenously applied adenosine receptor agonists in a concentration‐dependent fashion. The rank or‐der of potencies of adenosine receptor agonists, measured by the agonists' half‐maximal inhibitory concentrations, revealed that adenosine inhibited the numerical up‐regulation of β2integrins and shedding of L‐selectin most likely via an A2(a) receptor site. When extracellular concentrations of endogenously formed adenosine were enhanced by the nucleoside uptake inhibitor dipyridamole, up‐regulation of β2integrins, and shedding of L‐selectin was again inhibited. Both effects were reversed by the enzyme adenosine deaminase, which degrades active adenosine to inactive inosine, suggesting that endogenously formed adenosine may play an important role in the regulation of β2integrins and L‐selectin of human PMNL.

ISSN:0741-5400    

DOI:10.1002/jlb.59.5.671

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

Abstractlisteria monocytogenesis an intracellular bacterial pathogen. A single gene product, listeriolysin (LLO), is critical for the induction of protective immunity. We now show thatlisteriathat produce functional LLO augment Ia expression by macrophages and are better presented to a Th1, CD4+ anti‐listeriaT cell line. We used two genetically engineered strains oflisteriawhich differed only in their ability (Ly+) or inability (Ly‐) to produce functional LLO. Ia‐negative murine macrophages ingested either Ly+or Ly‐, and then were stimulated by interferon‐γ(IFN‐γ). Increasing numbers of live Ly+, but not Ly‐, augmented IFN‐γ‐induced Ia expression. Ly+by itself did not induce Ia expression. Heat‐killed Ly+and Ly‐did not augment IFN‐γ‐induced Ia expression. The abundance of Ia on the macrophage cell surface is one major determinant of antigen presentation to CD4+T cells. Consistent with their ability to augment Ia expression, Ly+were better presented than Ly‐to a CD4+, Th1, anti‐listeriaT cell line. When macrophages and T cells were from different inbred mouse strains, antigen presentation required identity at the Class II region of the MHC gene complex. This indicated that antigen presentation occurred via Ia molecules. The increased ability of macrophages to present Ly+is a product of the macrophage‐listeriainteraction, not a property of the T cell line 86. If Ia‐negative macrophages ingestedlisteriaand were then stimulated by IFN‐γ, Ly+was presented more efficiently than Ly‐. On the other hand, if Ia‐positive macrophages ingestedListeria, then Ly+and Ly‐were presented equally well to T cells. Altogether our data is consistent with the hypothesis that macrophages interact differently with Ly+, and that this contributes to the ability of only live Ly+‐to induce protective immunity.

ISSN:0741-5400    

DOI:10.1002/jlb.59.5.683

出版商:Wiley    

年代:1996

数据来源: WILEY