摘要:

It is increasingly appreciated that the part of an antibody not involved in the binding of antigen —the Fc region — plays an important biological role. It activates a variety of receptors not only on so‐called effector cells such as macrophages and granulocytes, but also on lymphocytes, and it can thereby modulate the immune response itself. Over the past 2 years much new information has been gained about the structure of such receptors, in large part through molecular genetics. In this review we describe the structure and some aspects of the function of the most complicated of the cellular Fc receptors so far identified: the receptor with high affinity for immunoglobulin E (IgE) on mast cells. The structure of its IgE‐binding chain is strikingly similar to the corresponding polypeptide of an immunoglobulin G receptor. Like the latter and like a receptor that binds polymeric immunoglobulin, segments of the protein resemble immunoglobulin sequences. It is surprising that other IgE‐binding proteins that putatively serve related functions have completely different structures.— Metzger, H.; Kinet, J.‐P. Howantibodies work: focus on Fc receptors.FASEB J.2: 3‐11; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.1.3275562

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Metastasis of cancer via the bloodstream is a major factor in the diagnosis, treatment, and prognosis of patients with cancer. Key events in hematogenous metastasis occur in the microvasculature. This is a brief, selective review of some interactions involving cancer cells and the microvasculature in pathological sequence, specifically:1) intravasation of cancer cells;2) the arrest of circulating cancer in the microvasculature;3) cancer cell trauma associated with arrest;4) microvascular trauma; 5) the inflammatory and6) coagulative responses associated with arrest; and7) the fate of arrested cancer cells. The evidence shows that in addition to providing routes for cancer cell dissemination and arrest sites for cancer cell emboli, the microvasculature, through a series of complex interactions with cancer cells, controls the efficiency of and acts as a rate regulator for the metastatic process.—Weiss, L.; Orr, F. W.; Honn, K. V. Interactions of cancer cells with the microvasculature during metastasis.FASEB J.2: 12‐21; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.1.3275560

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

In the biosynthesis of glycoproteins containing asparagine‐linked glycans, a number of regulatory factors must be involved in converting the single glycan precursor into the variety of different final structures observed in different eukaryotic species. Among these factors are the kind of glycan‐processing enzymes available in the Golgi apparatus of differenct cells, the specificity and regulatory properties of these enzymes, and the unique properties of the protein matrix in which a given glycan resides during the biosynthetic processing. In examining the role of this latter regulatory factor, we have considered a simplified model in which a few key steps are common to all cells, regardless of the nature of the processing enzymes available. The protein‐bound oligomannose precursor Man8GlcNAc2‐, arriving in the Golgi after the initial trimming in the endoplasmic reticulum (ER), first undergoes a series of preprocessing steps to yield Man5GlcNAc2‐in animals and plants or Man13‐15GlcNAc2‐ in yeast. At this stage the key commitment step — to process or not to process—determines whether the above intermediates will remain as unprocessed oligomannose structures or be initiated into a new series of reactions to yield processed structures characteristic of the organisms involved (complex or hybrid for vertebrates, polymannose for yeast, xylosylated glycans for plants and some invertebrates, or Man3GlcNAc2‐ structures for other invertebrates). It is proprosed that this commitment step, along with the obligatory preprocessing steps, is regulated primarily by each glycan's unique exposure on its protein matrix. Subsequent processing steps leading to complex or hybrid structures, fucosylation, extent of branching, and specific structures at the nonreducing terminals are most likely determined primarily by the enzyme makeup of the individual processing machineries, but with the protein matrix still playing a significant role.—Yet, M.‐G.; Shao, M.‐C.; Wold, F. Effects of the protein matrix on glycan processing in glycoproteins.FASEB J.2: 22‐31; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.1.3275561

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

As originally conceived, central neurotransmitters operated uniformly, exciting or inhibiting postsynaptic targets by receptors that activated passive ionic conductances. As the list of transmitter substances and their actions expanded, concepts of transmitter actions have broadened and grown more complex to include a variety of intramembranous and intracytoplasmic second messengers that can regulate both active and passive ionic conductances. Present‐day research directions center on further expansion of the lists of identified transmitter candidates, and on the more precise characterization of their sites and mechanisms of receptor regulation and transduction. Current research is also illuminating the means by which neurotransmitters act in a coordinated fashion to regulate common synaptic targets. Future directions will likely include new forms of interneuronal, intraneuronal, and glial signals, including lipids, steroids, and as‐yet‐undiscovered superfamilies of peptides and receptors. Although recent advances in understanding specific transmitters have been achieved largely through in vitro electrophysiological analyses, it is hoped that future research will recast these events in the context of the intact functioning brain. Neurotransmitters are likely to remain a productive focus of future research.— Bloom, F. E. Neurotransmitters: past, present, and future directions.FASEB J.2: 32‐41; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.1.2891578

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Most mammalian cells receive exogenous folate from the bloodstream in the form of 5‐methyltetrahydropteroylmonoglutamate (CH3‐H4PteGlu1). Because this folate derivative is a very poor substrate for folylpolyglutamate synthetase, the enzyme that adds glutamyl residues to intracellular folates, CH3‐H4PteGlu1must first be converted to tetrahydropteroylmonoglutamate (H4PteGlu1), 10‐formyltetrahydropteroylmonoglutamate (CHO‐H4PteGlu1), or dihydrofolate (H2folate), which are excellent substrates for folylpolyglutamate synthetase. Polyglutamylation is required both for retention of intracellular folates and for efficacy of folates as substrates for most folate‐dependent enzymes. Two enzymes are known that will react with CH3‐H4PteGlu1in vitro, methylenetetrahydrofolate reductase and methyltetrahydrofolate‐homocysteine methyltransferase (cobalamin‐dependent methionine synthase). These studies were performed to assess the possibility that methylenetetrahydrofolate reductase might catalyze the conversion of CH3‐H4PteGlu1to CH2‐H4PteGlu1. CH2‐H4PteGlu1is readily converted to CHO‐H4PteGlu1by the action of methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase, and these enzyme activities show very little preference for folylpolyglutamate substrates as compared with folylmono‐glutamates. We conclude from in vitro studies of the enzyme that methylenetetrahydrofolate reductase cannot convert CH3‐H4PteGlu1to CH2‐H4PteGlu1under physiological conditions and that uptake and retention of folate will be dependent on methionine synthase activity.—Green, J. M.; Ballou, D. P.; Matthews, R. G. Examination of the role of methylenetetrahydrofolate reductase in incorporation of methyltetrahydrofolate into cellular metabolism.FASEB J.2: 42‐47; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.1.3335280

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Substance P (SP) may play an important role in the interactions between the nervous system and the immune system. Astrocytes carry receptors for SP on their surfaces. We examined whether ligand‐induced receptor activation would lead to the release of arachidonic acid metabolites. SP (10−10‐10−8M) evokes the formation of prostaglandin E and thromboxane B2in a dose‐dependent manner. Structure‐activity studies disclosed that the COOH‐terminal peptide sequence of SP is primarily responsible for this biological activity. The generation by astrocytes of arachidonate‐derived proinflammatory and immunoregulatory compounds in response to SP receptor activation may be relevant to immunoinflammatory responses within the central nervous system and emphasizes the concept of neuroimmunomodulation.— Hartung, H.‐P.; Heininger, K.; Schäfer, B.; Toyka, K. V. Substance P and astrocytes: stimulation of the cyclooxygenase pathway of arachidonic acid metabolism.FASEB J.2: 48‐51; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.1.2446942

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Clonidine, a partial α2agonist, has been used empirically to alleviate opiate withdrawal symptoms, but the mechanism of its effects is not completely understood. We studied the interactions of opioid and adrenergic receptor agonists in the NG108‐15 cells, which are a model of opiate dependence. We determined that in these cells the adenylate cyclase (AC) [EC 4.6.1.1; ATP pyrophosphate‐lyase (cyclizing)] overshoot response to opioid or α2‐agonist withdrawal can be significantly attenuated or suppressed by the other agonist. Subsequently, the AC overshoot response can be triggered with the antagonist to the second agonist to which the cells were not dependent. These results demonstrate that convergent dependence to morphine and α2agonists can occur in a homogeneous cell population without neuronal loops. Therefore, the basic mechanisms that can account for convergent dependence in this model take place at the level of intracellular regulatory pathways that do not require neuronal networks.— Lee, S.; Rosenberg, C. R.; Musacchio, J. M. Cross‐dependence to opioid and α2‐adrenergic receptor agonists in NG108‐15 cells.FASEB J.2: 52‐55; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.1.2891579

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Selenate, a sulfation inhibitor, blocks the synthesis of heparan sulfate and chondroitin sulfate by cultured endothelial cells. In contrast, selenate does not affect the production of hyaluronic acid, a nonsulfated glycosaminoglycan. No differences in molecular weight, [3H]glucosamine/[35S]sulfuric acid ratios, or disaccharide composition were observed when the heparan sulfate synthesized by selenate‐treated cells was compared with that of control cells. The absence of undersulfated chains in preparations from cultures exposed to selenate supports the concept that, in the intact cell, the polymerization of heparan sulfate might be dependent on the sulfation of the saccharide units added to the growing glycosaminoglycan chain.—Dietrich, C. P.; Nader, H. B.; Buonassisi, V.; Colburn, P. Inhibition of synthesis of heparan sulfate by selenate: possible dependence on sulfation for chain polymerization.FASEB J.2: 56‐59; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.1.2961646

出版商:Wiley    

年代:1988

数据来源: WILEY