Molecular basis of the neutrophil glycoprotein NB1 (CD177) involved in the pathogenesis of immune neutropenias and transfusion reactions

Kissel, Karin; Santoso, Sentot; Hofmann, Christine; Stroncek, David; Bux, Jürgen

doi:10.1002/1521-4141(200105)31:5<1301::aid-immu1301>3.0.co;2-j

Cited by 88 publications

(99 citation statements)

References 38 publications

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“…This gene has granulocytespecific antigen function and is upregulated upon neutrophil activation by peptides derived from bacterial protein degradation, internalization upon cross-linking, and activation of the respiratory burst after antigen-antibody binding, suggesting a receptor function. 32 However, little is known about CD177 function. Antibodies to CD177 can cause a variety of disorders, including alloimmune neonatal neutropenia, autoimmune neutropenia, immune neutropenia after bone marrow transplantation, drug-induced immune neutropenia, transfusion-related lung injury, essential thrombocythemia, and myeloproliferative diseases.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

et al. 2014

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BACKGROUND: Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences. METHODS: This was a prospective observational double-cohort study conducted in VLBW (<1500 g) infants with culture-positive bacterial sepsis and non-septic matched controls. Blood samples were collected as soon as clinical signs of sepsis were identified and before antibiotics were initiated. Total RNA was processed for genome-wide expression analysis using Affymetrix gene arrays. RESULTS: During a 19-month period, 17 septic VLBW infants and 19 matched controls were enrolled. First, a three-dimensional unsupervised principal component analysis based on the entire genome (28 000 transcripts) identified 3 clusters of patients based on gene expression patterns: Gram-positive sepsis, Gram-negative sepsis, and noninfected control infants. Furthermore, these groups were confirmed by using analysis of variance, which identified a transcriptional signature of 554 of genes. These genes had a significantly different expression among the groups. Of the 554 identified genes, 66 belonged to the tumor necrosis factor and 56 to cytokine signaling. The most significantly overexpressed pathways in septic neonates related with innate immune and inflammatory responses and were validated by real-time reverse transcription polymerase chain reaction. CONCLUSIONS: Our preliminary results suggest that genome-wide expression profiles discriminate septic from nonseptic VLBW infants early in the neonatal period. Further studies are needed to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

et al. 2014

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“…We and others elucidated its primary structure by sequencing the NB1 and PRV-1 genes, which later turned out to be two alleles of a single CD177 gene (3)(4)(5). The surface expression of CD177 is unique in that only a subpopulation of neutrophils expresses this protein on the cell surface, with the mean size of the CD177-positive subpopulation ranging from 45% to 65% (2,6).…”

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confidence: 99%

“…It has been reported that CD177 is up-regulated on the neutrophil surface upon stimulation, including during severe bacterial infections, and following granulocyte-colony-stimulating factor treatment (9). In addition, antibody-mediated clustering of CD177 primes the N-formyl-methionyl-leucyl-phenylalanine (fMLP) 3 -activated respiratory burst reaction of the neutrophil (8). Taken together, these observations make it reasonable to suppose that CD177 may be involved in processes of neutrophil-mediated host defense.…”

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confidence: 99%

The Neutrophil-specific Antigen CD177 Is a Counter-receptor for Platelet Endothelial Cell Adhesion Molecule-1 (CD31)

Sachs

Andrei-Selmer

Maniar

et al. 2007

Journal of Biological Chemistry

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213

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Human neutrophil-specific CD177 (NB1 and PRV-1) has been reported to be up-regulated in a number of inflammatory settings, including bacterial infection and granulocyte-colonystimulating factor application. Little is known about its function. By flow cytometry and immunoprecipitation studies, we identified platelet endothelial cell adhesion molecule-1 (PECAM-1) as a binding partner of CD177. Real-time proteinprotein analysis using surface plasmon resonance confirmed a cation-dependent, specific interaction between CD177 and the heterophilic domains of PECAM-1. Monoclonal antibodies against CD177 and against PECAM-1 domain 6 inhibited adhesion of U937 cells stably expressing CD177 to immobilized PECAM-1. Transendothelial migration of human neutrophils was also inhibited by these antibodies. Our findings provide direct evidence that neutrophil-specific CD177 is a heterophilic binding partner of PECAM-1. This interaction may constitute a new pathway that participates in neutrophil transmigration.CD177 (NB1 and PRV-1) is a 58-to 64-kDa glycosylphosphatidylinositol-anchored glycoprotein expressed exclusively by neutrophils, neutrophilic metamyelocytes, and myelocytes, but not by any other blood cells (1, 2). We and others elucidated its primary structure by sequencing the NB1 and PRV-1 genes, which later turned out to be two alleles of a single CD177 gene (3-5). The surface expression of CD177 is unique in that only a subpopulation of neutrophils expresses this protein on the cell surface, with the mean size of the CD177-positive subpopulation ranging from 45% to 65% (2, 6).CD177 has been well studied as a target antigen in immunemediated disorders. During pregnancy, women with a CD177 null phenotype are prone to produce alloantibodies against CD177 that cross the placenta, react with fetal neutrophils, and cause neutropenia of the newborn. This mechanism let to the initial discovery of the NB1 antigen in 1971 (7). Alloantibodies to CD177, present in blood products obtained from immunized donors, have also been implicated as mediators of transfusionrelated acute lung injury (8).Although well characterized as an immunotarget, the function of CD177 is largely unknown. It has been reported that CD177 is up-regulated on the neutrophil surface upon stimulation, including during severe bacterial infections, and following granulocyte-colony-stimulating factor treatment (9). In addition, antibody-mediated clustering of CD177 primes the N-formyl-methionyl-leucyl-phenylalanine (fMLP) 3 -activated respiratory burst reaction of the neutrophil (8). Taken together, these observations make it reasonable to suppose that CD177 may be involved in processes of neutrophil-mediated host defense. One preliminary study suggests a participation of CD177 in neutrophil-endothelial cell interaction (10). The latter observation is in line with the fact that CD177, as a member of the leukocyte antigen-6 superfamily, shares a similar structure with the urokinase plasminogen activator receptor (11). Urokinase plasminogen activator receptor is expr...

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“…The glycoprotein has two cysteine-rich domains and three N-linked glycosylation sites. Homology of the cysteine-rich domains suggests that CD177 belongs to the Ly-6/uPAR/snake-toxin family of proteins (Kissel et al 2001). Kissel et al (2001) sequenced the gene encoding HNA-2a and found it to be located on chromossome 19q13.2.…”

Section: Biochemistry and Molecular Basismentioning

confidence: 99%

“…Homology of the cysteine-rich domains suggests that CD177 belongs to the Ly-6/uPAR/snake-toxin family of proteins (Kissel et al 2001). Kissel et al (2001) sequenced the gene encoding HNA-2a and found it to be located on chromossome 19q13.2. In addition, there is a pseudogene homologous to exons 4 through 9 that is located adjacent to the HNA-2a gene, but oriented in the opposite direction.…”

Section: Biochemistry and Molecular Basismentioning

confidence: 99%

Human neutrophil alloantigens systems

Moritz

Norcia

Cardone

et al. 2009

An. Acad. Bras. Ciênc.

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Neutrophil alloantigens are involved in a variety of clinical conditions including immune neutropenias, transfusionrelated acute lung injury (TRALI), refractoriness to granulocyte transfusions and febrile transfusion reactions. In the last decade, considerable progress has been made in the characterization of the implicated antigens. Currently, seven antigens are assigned to five human neutrophil antigen (HNA) systems. The HNA-1a, HNA-1b and HNA-1c antigens have been identified as polymorphic forms of the neutrophil Fcγ receptor IIIb (CD16b), encoded by three alleles. Recently, the primary structure of the HNA-2a antigen was elucidated and the HNA-2a-bearing glycoprotein was identified as a member of the Ly-6/uPAR superfamily, which has been clustered as CD177. The HNA-3a antigen is located on a 70-95 kDa glycoprotein; however, its molecular basis is still unknown. Finally, the HNA-4a and HNA-5a antigens were found to be caused by single nucleotide mutations in the α M (CD11b) and α L (CD11a) subunits of the leucocyte adhesion molecules (β 2 integrins). Molecular and biochemical characterization of neutrophil antigens have expanded our diagnostic tools by the introduction of genotyping techniques and immunoassays for antibody identification. Further studies in the field of neutrophil immunology will facilitate the prevention and management of transfusion reactions and immune diseases caused by neutrophil antibodies.

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Molecular basis of the neutrophil glycoprotein NB1 (CD177) involved in the pathogenesis of immune neutropenias and transfusion reactions

Cited by 88 publications

References 38 publications

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

The Neutrophil-specific Antigen CD177 Is a Counter-receptor for Platelet Endothelial Cell Adhesion Molecule-1 (CD31)

Human neutrophil alloantigens systems

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