bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin-mediated signaling in human neutrophil functioning
Authors: Williams Mark A , Solomkin Joseph S 
Published: January 2018

Abstract
Integrins are important signal transducers for virtually all neutrophil functions. Although a variety of signals ultimately result in integrin activation, the intracellular targets of integrin-initiated signals are poorly delineated to date. Polymorphonuclear (PMN) leukocyte responses to inflammation are dependent on both the stimulants and the extracellular environment encountered. Integrin ligation, by cell-cell or cell-matrix interactions, activates a variety of signaling cascades. These events dictate the nature of PMN responses to the encountered stimulus. The complex system of effector molecule recruitment and permissive signaling by integrins serves to strictly regulate PMN functions such as cell adhesion, motility, oxidant production, and protein synthesis. Moreover, there is evidence that cross-talk between integrins exists to prime integrin populations for subsequent functioning. This review summarizes the current understanding of signaling mechanisms for integrin priming and activation. In this connection, the role of specific signaling molecules in key PMN functions are examined. J. Leukoc. Biol. 65: 725–736; 1999.
No detectable NO synthesis from L-arginine or NG-hydroxy-L-arginine in fMLP-stimulated human blood neutrophils despite production of nitrite, nitrate, and citrulline from NG-hydroxy-L-arginine
Authors: Holm Päivi , Kankaanranta Hannu , Oja Simo S , Knowles Richard G , Moilanen Eeva 
Published: January 2018

Abstract
Nitric oxide (NO) is a well-documented effector molecule in rodent phagocytes but its synthesis in human neutrophils has been controversial. In this study, NO production in human neutrophils activated by chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) was measured in the presence of l-arginine (l-Arg) and NG-hydroxy-l-arginine (OH-l-Arg), the precursor and intermediate amino acids in NO synthesis, respectively. Incubation of fMLP-activated neutrophils with OH-l-Arg resulted in a production of nitrite, nitrate, and citrulline that was greater than with unstimulated neutrophils but was not inhibited by the NOS inhibitors l-NMMA and l-NIO or the cytochrome P450 inhibitor troleandomycin and was not seen when OH-l-Arg was replaced with l-Arg. This nitrite, nitrate, and citrulline production was not associated with any detectable NO synthesis because no increases in cyclic GMP were observed in the presence of phosphodiesterase inhibitors and in the presence or absence of superoxide dismutase. Moreover, no increases in the formation of the reaction product of NO with superoxide, peroxynitrite, were observed on addition of either OH-l-Arg or l-Arg to activated neutrophils, as assessed either by dihydrorhodamine oxidation or protein nitration. This suggests that, in spite of the production of nitrite, nitrate, and citrulline, commonly used indicators of NO formation, normal human blood neutrophils, are not producing detectable amounts of either NO or peroxynitrite when stimulated with fMLP in the presence of OH-l-Arg. J. Leukoc. Biol. 66: 127–134; 1999.
Regulatory effects of interleukin-11 during acute lung inflammatory injury
Authors: Lentsch Alex B , Crouch Larry D , Jordan Jacqueline A , Czermak Boris J , Yun Edward C , Guo Renfeng , Sarma Vidya , Diehl Kathleen M , Ward Peter A 
Published: January 2018

Abstract
The role of interleukin-11 (IL-11) was evaluated in the IgG immune complex model of acute lung injury in rats. IL-11 mRNA and protein were both up-regulated during the course of this inflammatory response. Exogenously administered IL-11 substantially reduced, in a dose-dependent manner, the intrapulmonary accumulation of neutrophils and the lung vascular leak of albumin. These in vivo anti-inflammatory effects of IL-11 were associated with reduced NF-κB activation in lung, reduced levels of tumor necrosis factor α (TNF-α) in bronchoalveolar lavage (BAL) fluids, and diminished up-regulation of lung vascular ICAM-1. It is interesting that IL-11 did not affect BAL fluid content of the CXC chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-inducible neutrophil chemoattractant (CINC); the presence of IL-11 did not affect these chemokines. However, BAL content of C5a was reduced by IL-11. These data indicate that IL-11 is a regulatory cytokine in the lung and that, like other members of this family, its anti-inflammatory properties appear to be linked to its suppression of NF-κB activation, diminished production of TNF-α, and reduced up-regulation of lung vascular ICAM-1. J. Leukoc. Biol. 66: 151–157; 1999.
Intestinal inflammation in adhesion molecule-deficient mice: an assessment of P-selectin alone and in combination with ICAM-1 or E-selectin
Authors: McCafferty Donna-Marie , Smith C Wayne , Granger D Neil , Kubes Paul 
Published: January 2018

Abstract
Biopsy specimens from patients with inflammatory bowel disease have demonstrated an up-regulation of P-selectin, suggesting a role for P-selectin in intestinal inflammation. We examined the role of P-selectin in experimental intestinal inflammation using mice deficient in P-selectin alone or in combination with either ICAM-1 or E-selectin. Colitis was induced using acetic acid or trinitrobenzene sulfonic acid (TNBS). Damage scores and neutrophil infiltration 24 h post acetic acid were not different between wild-type and P-selectin- or P-selectin/ICAM-1-deficient mice, whereas P/E-selectin-deficient mice had enhanced leukocyte recruitment and damage. At 72 h an attenuation in damage scores and a slight decrease in neutrophil infiltration was observed in the P- and P/ICAM-deficient animals. The P/E-selectin-deficient mice maintained enhanced leukocyte recruitment and damage. In wild-type mice P-selectin expression was elevated 48 and 72 h post acetic acid-induced inflammation. Surprisingly, P-selectin or P-selectin/ICAM-1 deficiency did not improve the inflammation induced by TNBS over 7 days. In fact, increased mortality was observed. Anti-adhesion therapy may play only a limited, beneficial role and often a detrimental role in intestinal inflammation. J. Leukoc. Biol. 66: 67–74; 1999.
The leukocyte immunoglobulin-like receptors (LIRs): a new family of immune regulators
Authors: Fanger Neil A , Borges Luis , Cosman David 
Published: January 2018

Abstract
Identification of a counterstructure for the human cytomegalovirus-encoded major histocompatibility complex class I-related gene product, UL18, has led to the discovery of a novel family of immunoreceptors, termed leukocyte immunoglobulin-like receptors (LIRs). The LIRs are differentially expressed in cells of the dendritic cell, monocytic and lymphocytic lineages, and appear to mediate diverse roles in immune regulation. This review summarizes the expression, distribution, and signaling capacities of the LIRs and discusses possible roles of the LIRs in both inhibition and activation of the cellular responses. J. Leukoc. Biol. 66: 231–236; 1999.
Genetic engineering of dendritic cells to express immunosuppressive molecules (viral IL-10, TGF-β, and CTLA4Ig)
Authors: Lu Lina , Lee Wei-Chen , Takayama Takuya , Qian Shiguang , Gambotto Andrea , Robbins Paul D , Thomson Angus W 
Published: January 2018

Abstract
There is growing evidence that, in addition to their role as initiators of immune responses, dendritic cells (DC) can exhibit tolerogenic properties. Immature DC deficient in cell surface costimulatory/accessory molecules can prolong organ and pancreatic islet allograft survival, whereas in vitro manipulation of DC by exposure to a variety of factors (e.g., viral interleukin-10; CTLA4Ig) can confer tolerogenic properties on these cells. Genetic engineering of DC to express immunosuppressive molecules is, in theory, an attractive approach to the therapy of allograft rejection and possibly, autoimmune disorders. J. Leukoc. Biol. 66: 293–296; 1999.
Dendritic cells in genetic immunization
Authors: Takashima Akira , Morita Akimichi 
Published: January 2018

Abstract
Both humoral and cellular immune responses are inducible by inoculation of naked plasmid DNA encoding a polypeptide antigen. This new vaccination protocol, known as genetic immunization, has been used to initiate protective immunity against a variety of infectious pathogens and tumors in experimental animals. Dendritic cells (DC) are thought to play at least three distinct roles in genetic immunization: (1) MHC class II-restricted presentation of antigens secreted by neighboring, transfected cells, (2) MHC class I-restricted “cross” presentation of antigens released by neighboring, transfected cells, and (3) direct presentation of antigens by transfected DC themselves. Several new technologies have been developed recently in an attempt to improve the overall efficacy of genetic vaccination, as well as to regulate the type and class of resulting immune responses. These technologies include modification of plasmid DNA, co-delivery of genes encoding immunoregulatory molecules, and DC targeting. We will overview some of these new technologies in genetic immunization. J. Leukoc. Biol. 66: 350–356; 1999.
Regulation of leukocyte adherence and migration by glycosylphosphatidyl-inositol-anchored proteins
Authors: Sendo Fujiro , Araki Yoshihiko 
Published: January 2018

Abstract
Leukocyte extravasation is essential for subsequent inflammation and the immune response. Extravasation can be divided into at least three steps; rolling, firm adhesion, and transendothelial migration. Although the mechanisms involved in the first two steps have been fairly well documented, the last step is complex and largely remains to be clarified. This review focuses on the possible role of GPI-anchored proteins on leukocytes in the regulation of their transendothelial migration. In addition to regulation by urokinase and its receptor, which has been regarded as the main modulator, we draw attention to a novel GPI-anchored protein (GPI-80) on human phagocytes that may be involved in regulating leukocyte adhesion and migration. The high degree of homology of GPI-80 with vanin-1, which is expressed on vascular tissues and is involved in prethymic cell homing into the thymus, raises the possibility that there is a family of molecules, including GPI-80 and vanin-1, that may be involved in leukocyte transendothelial migration. The possible role of soluble GPI-anchored proteins in this process is also discussed. J. Leukoc. Biol. 66: 369–374; 1999.
Endogenous IL-15 might be responsible for early protection by natural killer cells against infection with an avirulent strain of Salmonella choleraesuis in mice
Authors: Hirose Kenji , Nishimura Hitoshi , Matsuguchi Tetsuya , Yoshikai Yasunobu 
Published: January 2018

Abstract
Interleukin (IL)-15 is a novel cytokine with growth factor activity for T cells, B cells, and natural killer cells (NK cells). We investigated the role of IL-15 in the host defense against infection with avirulent Salmonella choleraesuis strain 31N-1 cured of 50-kb virulent plasmid. IL-15 was abundantly expressed at transcription and protein levels in macrophages infected with S. choleraesuis 31N-1. The number of NK cells in the infected sites was increased during the course of infection coincident with IL-15 production. Anti-IL-15 mAb administration inhibited the emergence of NK cells and interferon-γ (IFN-γ) production in serum after infection with S. choleraesuis 31N-1 and concurrently impaired the clearance of the bacteria. These results suggested that IL-15 might be responsible for protection against avirulent S. choleraesuis infection at early stage of infection through activation of NK cells in the infected sites. J. Leukoc. Biol. 66: 382–390; 1999.
Neutrophil activation in sickle cell disease
Authors: Lard L R , Mul F P J , de Haas M , Roos D , Duits A J 
Published: January 2018

Abstract
Vascular occlusion is the main cause of the morbidity and mortality observed in patients with sickle cell disease (SCD). Increasing evidence indicates that (activated) neutrophils could play an important role in the initiation and propagation of vaso-occlusive processes in SCD. In this study, the activation state of neutrophils in sickle cell patients was analyzed by determining the level of expression of neutrophil antigens such as CD62L, CD11b, CD66b, CD63, and Fcγ receptors. We also analyzed plasma levels of lactoferrin, elastase, soluble (s)CD16 (sFcγRIII), and serum levels of soluble (s)CD62L (sL-selectin) as neutrophil activation markers in these patients. Significant differences were observed in the activation state of neutrophils in non-symptomatic sickle cell patients compared to healthy HbAA controls as exemplified by significant decrease in L-selectin expression, enhanced expression of CD64, and increased levels of soluble markers like sL-selectin, elastase, and sCD16. During vaso-occlusive crisis the differences were even more pronounced. These results show neutrophils to be activated in sickle cell patients, suggesting a role of importance in the pathophysiology of sickle cell disease. J. Leukoc. Biol. 66: 411–415; 1999.
Digestion of C1q collagen-like domain with MMPs-1, -2, -3, and -9 further defines the sequence involved in the stimulation of neutrophil superoxide production
Authors: Ruiz S , Henschen-Edman A H , Nagase H , Tenner A J 
Published: January 2018

Abstract
C1q, a subunit of the first component (C1) of the classical complement pathway, binds to neutrophils via its collagen-like region (C1q-CLR) stimulating superoxide production. We previously identified a region of C1q-CLR, defined by fragments generated by trypsin and endoLys-C digestion, that was required for triggering this respiratory burst. To further localize that critical site, purified human C1q was digested with pepsin to generate C1q-CLR, and subsequently cleaved with the matrix metalloproteinases, MMP-1, MMP-2, MMP-3, and MMP-9. Digestion of C1q-CLR with any of these MMPs did not alter the circular dichroism spectra, demonstrating that the fragments generated had maintained the secondary structure observed in the native molecule. All fragments retained the ability to trigger superoxide production by neutrophils. Analysis of the amino acid sequences of the purified cleavage products (none of which are identical to the published cleavage site specificities for these enzymes) demonstrated that it is the C-chain, but not the A-chain of C1q, that is critical for stimulating this activity, and thus may be a target for future therapeutic intervention. J. Leukoc. Biol. 66: 416–422; 1999.
SLC/Exodus2/6Ckine/TCA4 induces chemotaxis of hematopoietic progenitor cells: differential activity of ligands of CCR7, CXCR3, or CXCR4 in chemotaxis vs. suppression of progenitor proliferation
Authors: Kim Chang H , Broxmeyer Hal E 
Published: January 2018

Abstract
Chemokines induce chemotaxis of hematopoietic progenitor cells (HPC), and suppress their proliferation. In this study we report that SLC/Exodus2/6Ckine/TCA4 (hereafter termed SLC) is a chemoattractant for human CD34+ HPC. SLC mainly induces preferential chemotaxis of macrophage progenitors. We examined the chemotactic activity of CXCR3 ligands on CD34+ HPC because it has been reported that SLC is a potential ligand of CXC chemokine receptor, CXCR3, in addition to a CC chemokine receptor, CCR7. It was found that the CXCR3 ligands, MIG and interferon-γ inducible protein-10 (IP-10), unlike SLC, did not induce chemotaxis of CD34+ HPC. In this regard, CCR7 ligands (SLC and CKβ-11), but not IP-10 and MIG, induce actin polymerization in CD34+ cells. On the other hand, CCR7 ligands and CXCR3 ligands, but not the CXCR4 ligand SDF-1, showed inhibitory activity for proliferation of myeloid progenitor cells. Our results suggest that SLC is a potential trafficking factor for HPC, and that chemokines that bind CCR7, CXCR4, and CXCR3 have differential biological activities on HPC in terms of suppression and chemotaxis. J. Leukoc. Biol. 66: 455–461; 1999.
Transcriptional control of the human MCP-2 gene promoter by IFN-γ and IL-1β in connective tissue cells
Authors: van Coillie Els , van Aelst Ilse , Fiten Pierre , Billiau Alfons , van Damme Jo , Opdenakker Ghislain 
Published: January 2018

Abstract
Human monocyte chemotactic protein-2 (MCP-2) is a member of the CC chemokine family. It is produced by mononuclear leukocytes, diploid fibroblasts, and tumor cells after induction with IL-1β or IFN-γ. To understand the transcriptional regulation of the gene, we have analyzed the structure and function of the promoter region. The sequence of the 5′-flanking region was determined and the transcription start site was found to be located at 68 nucleotides upstream of the ATG translation start codon. 5′-Deletion mutants were generated and transfected into E6SM diploid fibroblasts and MG-63 osteosarcoma cells. Expression was measured by luciferase assay in transfected unstimulated cells and after stimulation with IL-1β, IFN-γ, or a combination. The region between nucleotides -143 and -73 (relative to the transcription initiation site), containing putative cis-elements for GATA-1, H-APF1, AP-1, and GAS, is important for basal transcription levels in both cell lines. Stimulation for 18 h with IL-1β alone failed to affect expression of any of the constructs both in diploid fibroblasts and in osteosarcoma cells. In both cell lines IFN-γ increased the activity of all mutants that possessed the region between -340 and -301. In MG-63 cells, stimulation with the combination of IL-1β and IFN-γ caused an additional increase in expression of the constructs from -340 onward. Finally, the presence of transcription factors in nuclear extracts of MG-63 cells and their specificity to bind to various oligonucleotide probes in this [-340; -301] region were evidenced by electromobility shift assays. These results show that IFN-γ, produced by lymphocytes and NK cells, induces the transcription of the MCP-2 gene in fibroblasts and thereby can indirectly contribute to recruitment of various leukocyte cell types to inflammatory sites. J. Leukoc. Biol. 66: 502–511; 1999.
Ly-49 receptor expression and functional analysis in multiple mouse strains
Authors: Ortaldo John R , Mason Anna T , Winkler-Pickett Robin , Raziuddin Arati , Murphy William J , Mason Llewellyn H 
Published: January 2018

Abstract
We present data on the strain distribution and functional characteristics of the Ly-49 receptors A, C/I, D, and G2 on DX5+ natural killer (NK) cells. We have examined tyrosine phosphorylation of the Ly-49 molecules, regulation of NK cytotoxic functions, and in vivo marrow rejection capability. The flow cytometry results demonstrate a diverse and complex pattern of expression of the Ly-49 receptors in the 11 strains examined. The vast majority of NK cells express Ly-49s, although some NK1.1+ CD3+ cells also express these receptors. The results of our functional analysis indicate that H-2Dd was able to inhibit the function of Ly-49G2+ NK cells, not only in B6 mice, but also by NK cells derived from several haplotypes. The examination of Ly-49 receptor tyrosine phosphorylation, which is a biochemical measure of inhibitory function, was consistently observed in the 11 mouse strains examined. In contrast, analysis of Ly-49D function suggests its expression appears to be more restricted and that H-2Dd is an activating ligand for this receptor. In addition, the in vivo examination of both inhibitory (Ly-49G2) and activating (Ly-49D) receptors demonstrated regulatory roles of these class I binding receptors in marrow transplantation. J. Leukoc. Biol. 66: 512–520; 1999.
Inflammatory processes in a murine model of intra-abdominal abscess formation
Authors: Finlay-Jones John J , Davies Kate V L , Sturm Lana P , Kenny Peter A , Hart Prue H 
Published: January 2018

Abstract
Abscess formation has been viewed as a host defense strategy to contain the spread of infection. However, abscesses are also serious and life-threatening manifestations of persisting microbial infection. The initiation of abscess formation, both clinically and experimentally, involves the release of bacteria and an abscess-potentiating agent (e.g., fecal fiber or an analog) into a sterile site, with host defense mechanisms being unable to eliminate the infecting organisms. Abscess formation is aided by a combination of factors that share a common feature: impairment of phagocytic killing and hence clearance of microorganisms. These include bacterial virulence factors (e.g., capsule formation, succinic acid production); complement activation by the abscess potentiating agent; fibrin deposition; and microbial sequestration within abscess neutrophils. Recruitment of cells into the peritoneal cavity follows mast cell activation in the pathogenesis of infection: histamine and tumor necrosis factor α can be detected in the peritoneal cavity within minutes of challenge with an abscess-inducing mixture. However, the role of mast cells in host defense is made less clear by the finding of diminished abscess formation (but no mortality or increased morbidity) in mast-cell-depleted mice. This may indicate that mast cell products have a role in not only the initiation of an inflammatory response but also the promotion of fibrin deposition and abscess formation. J. Leukoc.Biol. 66: 583–587; 1999.
Characterization of the biosynthesis, processing, and sorting of human HBP/CAP37/azurocidin
Authors: Lindmark Anders , Garwicz Daniel , Rasmussen Poul B , Flodgaard Hans , Gullberg Urban 
Published: January 2018

Abstract
Azurocidin is a multifunctional endotoxin- binding serine protease homolog synthesized during the promyelocytic stage of neutrophil development. To characterize the biosynthesis and processing of azurocidin, cDNA encoding human preproazurocidin was stably transfected to the rat basophilic leukemia cell line RBL-1 and the murine myeloblast-like cell line 32D cl3; cell lines previously utilized to study the related proteins cathepsin G and proteinase 3. After 30 min of pulse radiolabeling, two forms of newly synthesized proazurocidin (34.5 and 37 kDa), differing in carbohydrate content but with protein cores of identical sizes, were recognized. With time, the 34.5-kDa form disappeared, while the 37-kDa form was further processed proteolytically, as judged by digestion with N-glycosidase F. Conversion of high-mannose oligosaccharides into complex forms was shown by acquisition of complete resistance to endoglycosidase H. Radiosequence analysis demonstrated that the amino-terminal seven amino acid propeptide of proazurocidin was removed in a stepwise manner during processing; initial removal of five amino acids was followed by cleavage of a dipeptide. Presence of the protease inhibitors Gly-Phe-diazomethyl ketone, bestatin, or leupeptin inhibited only the cleavage of the dipeptide, thus indicating the involvement of at least two amino- terminal processing enzymes. Translocation of azurocidin to granules was shown by subcellular fractionation. Similar results, with efficient biosynthesis, processing, and targeting to granules in both cell lines, were obtained with a mutant form of human preproazurocidin lacking the amino-terminal heptapropeptide. In conclusion, this investigation is an important addition to our previous studies on related azurophil granule proteins, and provides novel information concerning the biosynthesis and distinctive amino-terminal processing of human azurocidin. J. Leukoc. Biol. 66: 634–643; 1999.