C1q Receptors: Regulating Specific Functions of Phagocytic Cells

Tenner, Andrea J.

doi:10.1016/s0171-2985(98)80031-4

Cited by 57 publications

(33 citation statements)

References 64 publications

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“…Because allograft rejection occurs at ϳ7.8 days in our experimental protocol, these genes are highly up-regulated immediately before the time of rejection. Genes included in cluster 0 are IP-30 (40), Mac-2, a macrophage cell surface protein that binds extracellular matrix (41,42), monopolar spindle 1, AP50, a component of the CTLA-4 signaling complex (43,44), and C1q (identified by four different probes), which is a C-type lectin member of the collectin family important in innate immunity and up-regulated in the serum following renal transplantation (45,46). Our results suggest that complement may be important in allogeneic rejections.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Innate and Adaptive Phases of Allograft Rejection by Cluster Analysis of Transcriptional Profiles

Christopher

Mueller

et al. 2002

The Journal of Immunology

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Both clinical and experimental observations suggest that allograft rejection is a complex process with multiple components that are, at least partially, functionally redundant. Studies using graft recipients deficient in various genes including chemokines, cytokines, and other immune-associated genes frequently produce a phenotype of delayed, but not indefinitely prevented, rejection. Only a small subset of genetic deletions (for example, TCRα or β, MHC I and II, B7-1 and B7-2, and recombinase-activating gene) permit permanent graft acceptance suggesting that rejection is orchestrated by a complex network of interrelated inflammatory and immune responses. To investigate this complex process, we have used oligonucleotide microarrays to generate quantitative mRNA expression profiles following transplantation. Patterns of gene expression were confirmed with real-time PCR data. Hierarchical clustering algorithms clearly differentiated the early and late phases of rejection. Self-organizing maps identified clusters of coordinately regulated genes. Genes up-regulated during the early phase included genes with prior biological functions associated with ischemia, injury, and Ag-independent innate immunity, whereas genes up-regulated in the late phase were enriched for genes associated with adaptive immunity.

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Section: Discussionmentioning

confidence: 99%

Analysis of the Innate and Adaptive Phases of Allograft Rejection by Cluster Analysis of Transcriptional Profiles

Christopher

Mueller

et al. 2002

The Journal of Immunology

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“…The serum protein, C1Inhibitor, regulates the enzymatic activity of C1r and C1s by binding covalently into the active site of the enzymes. The C1rCls-C1Inhibitor 2 complex then dissociates from C1q-exposing regions of the collagen-like domain of C1q, which are able to interact with cell surface molecules inducing cellspecific responses [2]. Examples of those C1q-induced functions are the enhancement of phagocytic capacity in monocytes, culture-derived macrophages and neutrophils [3][4][5], and the stimulation of oxidative metabolism in neutrophils [6], eosinophils [7], and vascular smooth muscle cells [8].…”

Section: Introductionmentioning

confidence: 99%

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

Ruiz

Henschen-Edman

Nagase

et al. 1999

Journal of Leukocyte Biology

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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.

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“…Protein sequence analysis predicted that CD93 is composed of 652 amino acids with a signal peptide, C-type carbohydrate recognition domain, five epidermal growth factor (EGF) domains with at least three likely calcium binding domains, a potential N-linked glycosylation site, a transmembrane domain and a cytoplasmic tail with a potential tyrosine kinase phosphorylation site (31). Western blotting analysis revealed CD93 to be a 126-kDa protein in reducing conditions and a 90 to 100-kDa protein in non-reducing conditions (13,30,38). Glycosylation studies showed human CD93 to be a heavily O-glycosylated type I transmembrane protein consisting of unique C-type lectin domains displaying a 68% homology to rat or mouse AA4 antigen (6,7).…”

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confidence: 99%

Regulation of CD93 Cell Surface Expression by Protein Kinase C Isoenzymes

Ikewaki

Kulski

Inoko

2006

Microbiology and Immunology

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Human CD93, also known as complement protein 1, q subcomponent, receptor (C1qRp), is selectively expressed by cells with a myeloid lineage, endothelial cells, platelets, and microglia and was originally reported to be involved in the complement protein 1, q subcomponent (C1q)‐mediated enhancement of phagocytosis. The intracellular molecular events responsible for the regulation of its expression on the cell surface, however, have not been determined. In this study, the effect of protein kinases in the regulation of CD93 expression on the cell surface of a human monocyte‐like cell line (U937), a human NK‐like cell line (KHYG‐1), and a human umbilical vein endothelial cell line (HUV‐EC‐C) was investigated using four types of protein kinase inhibitors, the classical protein kinase C (cPKC) inhibitor Go6976, the novel PKC (nPKC) inhibitor Rottlerin, the protein kinase A (PKA) inhibitor H‐89 and the protein tyrosine kinase (PTK) inhibitor herbimycin A at their optimum concentrations for 24 hr. CD93 expression was analyzed using flow cytometry and glutaraldehyde‐fixed cellular enzyme‐linked immunoassay (EIA) techniques utilizing a CD93 monoclonal antibody (mAb), mNI‐11, that was originally established in our laboratory as a CD93 detection probe. The nPKC inhibitor Rottlerin strongly down‐regulated CD93 expression on the U937 cells in a dose‐dependent manner, whereas the other inhibitors had little or no effect. CD93 expression was down‐regulated by Go6976, but not by Rottlerin, in the KHYG‐1 cells and by both Rottlerin and Go6976 in the HUV‐EC‐C cells. The PKC stimulator, phorbol myristate acetate (PMA), strongly up‐regulated CD93 expression on the cell surface of all three cell‐lines and induced interleukin‐8 (IL‐8) production by the U937 cells and interferon‐γ (IFN‐γ) production by the KHYG‐1 cells. In addition, both Go6976 and Rottlerin inhibited the up‐regulation of CD93 expression induced by PMA and IL‐8 or IFN‐γ production in the respective cell‐lines. Whereas recombinant tumor necrosis factor‐α (rTNF‐α) slightly up‐regulated CD93 expression on the U937 cells, recombinant interleukin‐1β (rIL‐1β), recombinant interleukin‐2 (rIL‐2), recombinant interferon‐γ (rIFN‐γ) and lipopolysaccharide (LPS) had no effect. Taken together, these findings indicate that the regulation of CD93 expression on these cells involves the PKC isoenzymes.

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C1q Receptors: Regulating Specific Functions of Phagocytic Cells

Cited by 57 publications

References 64 publications

Analysis of the Innate and Adaptive Phases of Allograft Rejection by Cluster Analysis of Transcriptional Profiles

Analysis of the Innate and Adaptive Phases of Allograft Rejection by Cluster Analysis of Transcriptional Profiles

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

Regulation of CD93 Cell Surface Expression by Protein Kinase C Isoenzymes

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