摘要:

AbstractPolymorphonuclear leukocytes (PMN) exposed to highly purified human lactoferrin (from colostrum) exhibit an increased random motility (at least 2.5‐fold) and are primed to produce more superoxide [12.1 ± 1.2 nmol O2‐/min/106PMN preincubated with lactoferrin (0.5 mg/ml) against 6.4 ± 2.3 with cells without lactoferrin after FMLP stimulation]. The action of lactoferrin seemed to be specific, because it could be abolished by simultaneous addition of antilactoferrin antibody. Addition of transferrin and iron salts to PMN was without effect. Between iron‐poor and iron‐saturated lactoferrin there was no difference in influence on PMN function except for a higher FMLP stimulated superoxide production by iron‐saturated lactoferrin. Aggregation, degranulation (β‐glucuronidase, lysozyme), and bacterial killing were not influenced by lactoferrin. Incubation of monocytes and monocyte‐derived macrophages with lactoferrin did not alter their motility or their superoxide production rates. Our findings indicate that PMN become more effective after exposure to lactoferrin by having a greater motility and producing superoxide at a faster rate.

ISSN:0741-5400    

DOI:10.1002/jlb.49.5.427

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractThe mAb ED3 recognizes a subpopulation of rat macrophages, with a highly restricted tissue distribution. The tissue distribution as well as the in vitro expression of the ED3 antigen and of the sheep erythrocyte receptor (SER), binding unopsonized erythrocytes in the mouse, are very similar. This receptor has almost the same binding characteristics, although a different tissue distribution, as the sialic acid binding receptor (SAR), binding ganglioside‐coated erythrocytes in the rat In this study we summarize the available literature concerning these sialic acid binding receptors (SER and SAR). Furthermore we have identified ED3 as SER by inhibition studies of erythrocyte binding with mAb ED3, as well as by the newly developed equivalents ED16 and ED17. We also show that light trypsin treatment of alveolar macrophages, expressing SAR, results in SER‐like activity. This obtained SER‐like activity could not be blocked by the mAb ED3, indicating that SER and SAR are different receptors. It appears that rat macrophages can express two receptors for sialylated glycoconjugates, a high‐affinity receptor SER, recognized by mAb ED3, and a low‐affinity receptor SAR, not recognized by mAb ED3.

ISSN:0741-5400    

DOI:10.1002/jlb.49.5.434

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractThe effect of herpes simplex virus type 2 (HSV‐2) infection on the oxidative response in infant and adult rabbit alveolar macrophages (AM) was studied using either phorbol myristate acetate (0.5 μg PMA/ml) or latex (250 μg/ml) as eliciting agents in a chemiluminescence (CL) assay. Results indicated that uninfected infant AM responded to a latex‐elicited but not PMA‐elicited CL response. HSV‐2 infection (moi=1.0) of infant AM for 2 hr at 37° did not alter the PMA or latex‐elicited CL responses. In contrast, uninfected adult AM exhibited a markedly increased CL response when elicited with either PMA or latex. HSV‐2 infection (moi=1) of adult AM for 2 hr further increased both PMA‐ and latex‐elicited CL responses. Increasing the moi to 10 inhibited both PMA‐ and latex‐elicited CL responses. Incubation of uninfected control and HSV‐2 infected adult AM for 18 hr at 37° resulted in spontaneous priming of the cells for increased CL responses. In the absence of PMA HSV‐2 alone failed to elicit a CL response in adult AM. Infection with heat‐inactivated HSV‐2 (moi=1.0 before heat inactivation) did not prime adult AM for enhanced CL responses. AM from BCG immunized adult rabbit produced a considerably higher level CL response that nonimmunized AM; however, HSV‐2 infection of these cells did not further enhance the response. In summary, these data indicate that adult AM but not infant AM can be primed by active HSV‐2 infection for an increased CL response elicited by either PMA or latex.

ISSN:0741-5400    

DOI:10.1002/jlb.49.5.442

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractActivated polymorphonuclear neutrophils (PMN) and neutrophil activating mediators such as tumor necrosis factor‐α (TNF‐α) are thought to be involved in the pathophysiology of sepsis and multiple organ failure syndrome (MOFS). In critically ill patients at high risk for the development of septic syndrome (n= 17) peripheral blood PMN were assayed for O‐2and H2O2production after stimulation with phorbol myristate acetate (PMA, 40 nM). Serum TNF‐α levels were determined by ELISA. At the time of admission to the intensive care unit we found significant higher levels of TNF‐α (P= 0.0001) in the serum of patients finally developing sepsis correlating to higher respiratory burst capability in comparison to nonseptic patients. Additionally we were able to demonstrate a significant (P= 0.0016) lower dismutation rate of O‐2to H2O2in deceased patients in comparison to survivors. These results give further evidence that elevated levels of circulating TNF‐α and activated PMN play a significant role in the pathogenesis of septic syndrome in critically ill patients.

ISSN:0741-5400    

DOI:10.1002/jlb.49.5.449

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractTumor transplantation, major surgery, and injection of nonspecific irritants elicit inflammation locally while suppressing inflammation induced subsequently and at distant sites. Such systemic antiinflammation in rodents occurs via corticosterone‐independent and ‐dependent pathways. Based upon hormone measurements and the response to adrenalectomy, antiinflammation induced by irritants and certain surgical procedures is corticosterone independent while that which follows tumor transplantation is corticosterone dependent. However, injection of tumorous ascites stimulates both pathways since it contains two antiinflammatory factors: Factor A (molecular weight<2,000) does not alter hormone balance while Factor B (molecular weight 30,000–100,000) increases corticosterone levels and is corticosterone dependent. Desensitization of systemic antiinflammation develops rapidly regardless of whether it is corticosterone dependent (Factor B) or independent (Factor A or irritants). However, tumor transplantation resists desensitization possibly by inducing an immune response since lymphocytic mitogens prevent development of and break established desensitization. Nevertheless, abolition of tumor‐induced antiinflammation follows injection of tumorous ascites by a mechanism that involves Factor B suppression of the corticosterone response to the tumor while Factor A apparently raises the threshold at which physiological increases in corticosterone inhibit leukocyte emigration. We conclude that systemic antiinflammation is a general consequence of a localized inflammatory reaction and that desensitization of such antiinflammation develops rapidly. Recent evidence indicates that certain mediators of inflammation are proinflammatory when administered intradermally but antiinflammatory when given intravenously. Thus, systemic antiinflammation may arise when chemical mediators of inflammation generated by a local reaction gain access to the circulation.

ISSN:0741-5400    

DOI:10.1002/jlb.49.5.455

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractHigh‐affinity receptors for human IFN‐γ were analyzed using 13 different cells, including blood monocytes. Scatchard analysis showed one high‐affinity binding site for each cell. One cross‐linked complex between IFN‐γ and the receptor was detected, although their apparent molecular masses were variable in different cells, as also confirmed in immunoblots of membrane extracts. Variations in molecular masses were abolished if N‐linked glycosylation was absent. Stable tryptic fragments contained the intact binding site for IFN‐γ and antibody epitopes characteristic of the extracellular domain of the IFN‐γ receptor of Raji cells and were of different sizes only if glycosylated. In addition, Northern analysis showed the same mRNA encoding the high‐affinity IFN‐γ receptor in each cell analyzed. Thus, all cells including blood monocytes express the same high‐affinity IFN‐γ receptor protein. N‐linked sugars may give structural stability to the IFN‐γ receptor and are unlikely to be directly involved in IFN‐γ binding.

ISSN:0741-5400    

DOI:10.1002/jlb.49.5.462

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractThe ability of progressing tumors to regulate host physiology is an important consideration in our understanding of tumor‐host relationships. Previous data indicated that several lines of murine sarcoma cells produced one or more activities that were able to regulate bothIl‐1a andIl‐1 bgene transcription in macrophages (Mø). We now describe an indepth analysis using Northern analysis and bioassays and show that two of these tumors produce one or more activities that when incubated with peritoneal Mø result in the transcription of theIl‐a, Il‐1 b, Tnfa, andIl‐6 genes. Concordant with the Northern analyses was the finding that interleukin‐1 (IL‐1) and tumor necrosis factor (TNF) biological activities were detected in lysates of induced Mø, fixed Mø, and supernates of Mø cultures. Induction of gene expression was shown to be distinct from that induced by bacterial endotoxin or lipopolysaccharide by a number of criteria. The data suggest that tumor cell products may play an important role in regulating several host physiological processes, particularly those involvingIl‐1 a, Il‐1b, Tnf a, andIl‐6 gene expression.

ISSN:0741-5400    

DOI:10.1002/jlb.49.5.474

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractFunctional competence as well as phenotype heterogeneity of macrophages depend on the completion of their maturation pathway. Differentiation of committed myeloid progenitor cells is induced by colony‐stimulating factors (CSF), but no consistent data exist on which factor(s) induce the terminal maturation from the circulating blood monocyte to the mature macrophage. In vitro, monocyte to macrophage transformation occurs in the presence of serum and can be followed by the expression of the maturation‐associated antigens gp65‐MAX.1, gp68‐MAX.3, and CD51. We describe that the differentiation‐inducing activity in serum cannot be replaced by any of the known and available purified recombinant cytokines. In the absence of serum monocytes die in suspension cultures while surviving as non‐differentiating cells when cultured adherent to plastic. In serum‐free suspension cultures survival can be significantly improved by the addition of recombinant human macrophage (rhM)‐CSF whereas other cytokines do not. At any stage of serum‐free adherent culture, monocyte to macrophage differentiation can be induced rapidly by the addition of serum, whereas cytokines (rhM‐CSF, recombinant human granulocyte macrophage [rhGM]‐CSF, recombinant human granulocyte [rhG]‐CSF, recombinant human interleukin [rhIL]‐1, rhIL‐3, rhIL‐4, rhIL‐6, tumor necrosis factor [TNF]‐α, interferon [IFN]‐α, IFN‐γ) alone or in combination are not effective. Serum‐induced maturation, however, was suppressed in the presence of neutralizing anti‐M‐CSF antibodies. In addition to phenotype analysis, the secretory repertoire of rhM‐CSF cultured monocytes was analyzed in comparison to serum cultured monocytes which further characterized them to be immature cells, i.e., low release of maturation‐associated products such as α‐2‐macroglobulin, neopterin, fibronectin, and TNF‐α, but high IL‐6 secretion, an attribute of blood monocytes. We conclude that for monocyte survival in vitro the presence of endogenous M‐CSF and possibly other autocrine factors elicited by cell adherence are required for the induction of macrophage maturation; however, yet undefined additional factor(s) are necessary. They are present in serum and may act in conjunction with M‐CSF but are distinct from all known cytokines. Our in vitro system may be useful in the screening and discovery of these serum factor(s).

ISSN:0741-5400    

DOI:10.1002/jlb.49.5.483

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractThe neutrophil response to infection and inflammation includes membrane fusion or degranulation and activation of the membranous respiratory burst oxidase. The role of degranulation in the activation of the burst was explored in resting and activated cells. Exposed membrane proteins of intact cells were labeled with impermeant reagents. Phorbol ester‐activated neutrophils and enucleated cells which are granule depleted both exhibit increased labeling with [125l]lactoperoxidase over that of resting cells. The binding of antibodies to granule membranes by cells activated with phorbol ester or treated with cytochalasin B and lithium chloride were similarly increased. These data indicate that insertion of granule membrane into the cell membrane occurs during activation and enucleation of neutrophils.Hyperosmolarity, known to inhibit degranulation, also exhibited an inhibitory effect on the respiratory burst oxidase in the presence of phorbol ester or latex. Pre‐treatment of cells with phorbol ester followed by an increase in osmolarity, however, still resulted in activation. Temperatures below 17°C abruptly and simultaneously abolish degranulation and activation of the respiratory burst oxidase. Pre‐treatment of neutrophils with phorbol ester at 37°C, followed by measurement of oxidase activity at decreased temperatures, on the other hand, revealed a linear Arrhenius plot above and below 17°C. These results suggest that membrane fusion or degranulation is a step in activation of the respiratory burst.

ISSN:0741-5400    

DOI:10.1002/jlb.49.5.489

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractEpithelial and submucosal mesenchymal (SM) cells from normal human small intestine and colon could be directly infected by several strains of the human immunodeficiency virus (HIV). Macrophage‐derived virus strains were more potent than the HTLVIIIB prototype strain. Persistent release of virus over several months implies that the human gastrointestinal tract may serve as a site for primary infection and as a reservoir for the virus. Furthermore, HIV infection of SM cells may be an in vitro model of Kaposi's sarcoma.

ISSN:0741-5400    

DOI:10.1002/jlb.49.5.499

出版商:Wiley    

年代:1991

数据来源: WILEY