The Function Of Cxcr4 Receptor Depends On Lipid Raft Formation

The function of CXCR4 on HSPC is regulated at multiple levels (Figure 1). First, expression of CXCR4 is regulated at the transcriptional level by several factors (e.g., hypoxia)22-30. Second, CXCR4 as well as its ligand SDF-1, are subject to proteolytic degradation by some proteases (e.g., metalloproteinases (MMPs), dipetidylpeptidase CD26 , and carboxypeptidase) that are expressed in the hematopoietic microenvironment and serum31,32. Third, CXCR4 after interaction with SDF-1 is internalized...

Engraftment Of Hspc In C3deficient Mice

The early stages of BM seeding by HSPC, which precedes their proliferation differentiation, are collectively termed homing. Homing can be divided into several overlapping steps. CXCR4+ HSPC infused into PB have to respond to a chemotactic SDF-1 gradient in BM, attach to BM endothelium, transmigrate through the basal membrane in a metalloproteinase-dependent manner, and finally home to a niche where they have to subsequently survive, expand, and proliferate1,54. Thus, homing of HSPC to BM niches...

Immune Evasion The C3bspicevcp Interaction

Considerable effort has been placed in the field of antiviral vaccine design toward elucidating the mechanism by which certain herpes and orthopox viruses escape the host immune response, through structural and functional mimicry of complement regulatory proteins46. SPICE and VCP are two secreted viral homologs of complement regulatory proteins that bear CCP modules and mediate immune evasion in the host by interacting with C3b and preventing complement-mediated neutralization of virus47,48....

Discussion

In previous C3d-CR2 studies, CR2 binding has not been linked to the immune enhancement effects of C3d. In this study, in order to determine the specificity of the interaction between C3d and CR2, we directly assessed the adjuvant effect of a peptide representing the amino-acid sequence of one of the proposed CR2 binding sites on C3d (P28). The HIV-1 Envgp120 was conjugated to multimers of P28 and directly compared to elicitation of immune responses by Envgp120 conjugated to multimers of the...

Introduction

The complement system is a highly sophisticated host-defense system playing an important role in both innate and antibody-mediated immunity. Pathophysio-logical disregulation of the complement system, however, contributes to tissue damage in many clinical conditions, including ischemia-reperfusion injuries after myocardial infarction, interventional activation of complement in patients undergoing cardiopulmonary bypass, and immune-mediated diseases1-4. From these implications an urgent need for...

Potential Complementbased Therapeutics

If complement does contribute significantly to the progression of pathology in these and improved mouse models, many mechanistic questions would remain to be addressed. However, if correlations to changes in neuronal activity or behavior are determined, investigations of potential therapies directed at eliminating specific activation of CCP by fibrillar AB may be considered without complete knowledge of the downstream mechanisms. The development of complement inhibitors that can be used in...

Cellbound Complement Activation Products

The inconsistent results obtained from measures of soluble complement proteins and activation products have led us to consider measurement of cell-bound complement activation products CB-CAPs as biomarkers for SLE diagnosis and monitoring. This hypothesis was based upon the following rationale. First, serum C3 and C4 levels have no diagnostic utility and limited monitoring utility, and the inherent flaws in these measurements have been well documented, as described above. Second, measurement of...

Complementderived Dangertransmitters Shape Innate And Adaptive Immune Responses Following Physiological And

The immune system needs to distinguish between physiologic changes in the environment, e.g., physiologic cell death and the necessity to clear these cells without substantial inflammation and pathological changes that demand inflammation. In short, danger-sensing needs to translate into adequate dangertransmission that tailors the immune response. The complement system is well suited for this task as it releases a panel of bioactive cleavage fragments, the function of which is regulated by...

Function Of Ficolin

Carbohydrate Binding of Ficolin We previously reported that L-ficolin bound to GlcNAc in GlcNAc-BSA and complex-type oligosaccharide chains with GlcNAc residues linked to the tri-mannosyl core, but not to mannose-BSA or high mannose-type or hybrid-type oligosaccharides4. Unlike MBL, L-ficolin was able to bind to GlcNAc next to a terminal galactose in oligosaccharides. H-ficolin binds GlcNAc and GalNAc, but not mannose and lactose8. It agglutinates human erythrocytes coated with...

The Role Of Complement Deposition In Myelin Damage

The focus of most investigations was the role of the classical and alternative pathways of complement in EAE or MS, and almost all proteins have been studied one by one from C1 to C9. In the following section we summarize data obtained from mice with targeted or total depletion of complement, and studies on particular soluble C components. Cobra venom factor CVF is a protein isolated from cobra venom Naja naja or Naja haje , which forms a stable C3 convertase with factor B and depletes C3 from...

References

Samuels, R. C. Tiwari, A. Ghafoor, E. J. Feuer and M. J. Thun, Cancer statistics, CA Cancer J Clin 55 1 , 10-30 2005 . 2. R. A. Bok and E. J. Small, Bloodborne biomolecular markers in prostate cancer development and progression, Nat Rev Cancer 2 12 , 918-926 2002 . 3. G. Ronquist and M. Hedstrom, Restoration of detergent-inactivated adenosine triphosphatase activity of human prostatic fluid with concanavalin A, Biochim Bio-phys Acta 483 2 , 483-486 1977 . 4....

Clinical Indications For Complement Analysis

Ch50 Assay

Clinical and experimental evidence underlines the prominent role of complement in immunodeficiency disorders8 and in the pathogenesis of numerous inflammatory diseases including immune complex and autoimmune disorders, such as systemic lupus erythematosus9 and autoimmune arthritis10. Complement has also been implicated in neurodegenerative disorders, such as Alzheimer's disease11, multiple sclerosis12, and Guillain-Barr syndrome13. Complement activation after polytrauma substantially...

Results

Inhibition of Hemolytic Activity by gC1qR Normal human serum was first incubated with either buffer, BSA, or various concentrations of recombinant gC1q-R rgC1qR or soluble gC1qR sgC1q-R isolated from culture supernatants of Raji cells12. The residual hemolytic activity was measured by standard hemolytic assay. As shown in Figure 1, incubation of either soluble gC1qR or the recombinant form of gC1qR with NHS is able to inhibit complement hemolytic activity in a dose-dependent manner and...