Complement Receptor Gene Expression

The number of CR1 per erythrocyte varies between approximately 100 and 1000, and is genetically regulated by two alleles 1 . In comparison, leukocytes express between 10,000 and 50,000 CR1 on the surface membrane. Although the number of CR1 per erythrocyte is low, as compared to other cell types, the abundance of erythrocytes in the circulation means that erythrocytes are the major carriers of CR1. Surprisingly little is known about the transcriptional regulation of CR1 (Fig. 1). The only study...

Disease Associations of C1r and C1s

Deficiencies of C1r and C1s are rare but can cause severe disease conditions. The most common consequences of these deficiencies are systemic lupus erythematosus (SLE)-like syndromes and severe pyogenic infections. It has long been suggested that the SLE-like symptoms are the consequences of the inappropriate handling of immune complexes. Deficiency of C1r and C1s are almost exclusively coupled, probably due to the close physical proximity and the coordinated expression of the two genes (Morgan...

The Lectin Pathway in Health and Disease

The first study of linking recurrent infections to MBL deficiency was reported more than a decade ago (Super et al., 1989). Since then a large number of studies have been conducted on the association between MBL deficiency and the development or progression of various diseases, which have been extensively reviewed in recent years (Turner, 1998 Turner and Hamvas, 2000 Petersen et al, 2001 Turner, 2003). Three single nucleotide mutations in exon 1 of the mbl2 gene have been identified as the...

Connective Tissue Disease

Elevated levels of C5b-9 have been detected in the synovial fluids of patients with rheumatoid arthritis (Mollnes, 1986 Brodeur, 1991) and deposits of the same complex have been documented on the synovial membrane of these patients (Sanders, 1986) in amounts that are related to the degree of disease activity (Oleesky, 1991 Corvetta, 1992). Evidence has also been provided suggesting that part of this TCC is produced locally in the synovial tissues (Neumann, 2002). The critical role played by TCC...

Therapeutic Control Of

The findings from in vitro and in vivo experimental models that TCC is involved in cell and tissue damage has prompted an intensive search for therapeutic tools that could effectively neutralize the undesired biological effects of this complex. Peptides competing for the functionally active sites of the late components and monoclonal antibodies inhibiting their functional activities represent two important choices that have a potential application as therapeutic agents in clinical conditions...

Signaling Through DAF

Almost all studies of the signaling capability of DAF have utilised antibodies to cross-link the molecule on the surface of cells. Initial work over 10 years ago demonstrated that antibody-mediated cross-linking of DAF on neutrophils resulted in release of Ca2+ stores, activation of tyrosine kinases and activation of the oxidase response in addition monocytes demonstrated enhanced phagocytic activity when activated by DAF (101,102). There has been little follow-up to these initial studies,...

Hereditary C9 Deficiency

Initially C9 deficiency was thought to be rare and not associated with disease. Further study of C9 deficiencies, especially in ethnic Japanese, has demonstrated that the incidence of C9 deficiency in Japan is about 0.086 , much higher than in initial studies of other populations. Three cases of SLE have been reported in association with C9 deficiencies in Japan. The first reported patient had sicca syndrome accompanied by severe Raynaud's phenomenon (64). Serologic tests for ANA and dsDNA were...

Hereditary MBL Deficiencies

MBL protein deficiencies, which are a result of the gene mutations of the MBL gene, have been studied in SLE. Serum levels of MBL were measured in a study with 58 SLE, 92 HIV, 30 chronic liver disease, 20 rheumatoid arthritis, and 161 healthy controls (67). Severely decreased levels of serum MBL protein were found in 12 of SLE patients, 4 of HIV patients, 3 of liver disease patients, no RA patients, and 4 of healthy controls. In one study (68), 102 Caucasian SLE patients were compared to 136...

References

Reactions to radiocontrast media. Allergy and Asthma Proc. 2002 23 347-351 6. Laroche D., Aimone-Gastin I., Dubois F., Huet H., G.rard P., Vergnaud M.C., Mouton-Faivre C., Gu.ant J.L., Laxenaire M.C., Bricard H. Mechanisms of severe, immediate reactions to iodinated contrast material. Radiology 1998 209 183-190 7. Courvoisier S., Bircher A.J. Delayed-type hypersensitivity to a nonionic, radiopaque contrast medium. Allergy 1998 53 1221-1224 8. Szebeni J....

Hereditary C4 Deficiency

C4-deficient patients of two types have been characterized complete C4 deficiency, in which both the C4A and C4B protein products are absent, and partial C4 deficiencies, in which C4 levels are decreased and one or more of the genes for either C4A or C4B genes are missing. Complete C4 deficiency is rare among 25 reported patients 21 (84 ) had SLE or SLE-like disease (2937). Seventeen patients had skin rash, predominately with photosensitivity lupus band test were negative in four of the five...

Acquired C3 Deficiency and Systemic Lupus Erythematosus

A portion of patients with chronic mesangiocapillary glomerulonephritis will have associated depressed serum levels of C3. In a study of 21 patients with partial lipodystrophy, 17 were found to have low C3 with normal C4 and C2 concentrations (99). Seven had chronic mesangiocapillary glomerulonephritis. The patients with depressed C3 levels have been shown to have a protein in their sera capable of cleaving C3 in normal serum. This protein has been termed C3 nephritic factor (C3Nef) and has...

The Complex Roles of Anaphylatoxins in Allergic Asthma and Autoimmune Diseases

Heiko Hawlisch1, Marsha Wills-Karp2, Christopher L. Karp1, and Jorg Kohl1 1 Division of Molecular Immunology and 2 Division of Immunobiology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA Abstract Complement has a long-recognized role as a lytic effector system that protects against microbial pathogens as well as a mediator of acute and chronic inflammatory responses. Many of the inflammatory properties related to...

Complementdependent Loss Of Innate Immune Functions

Recent studies suggest that CLP-induced sepsis in rats leads to loss of innate immune functions (15,19). Innate immunity is defined as protective shield against invading micro-organisms or pathogens, with protective cell functions that do not require induction of an immune response, a primed cellular defense or a secondarily enhanced humoral immune response. It is well established during sepsis that leukocyte function is perturbed (reviewed, 3). Our own studies indicate that, in CLP rats, blood...

Modulation of Airway Smooth Muscle Contraction by Anaphylatoxins Potential Mechanisms

Among the various effector pathways of the asthmatic response, anaphylatoxins have long been recognized as potent contractile agonists for smooth muscle. Controversy exists, however, as to whether these effects are direct or secondary to the release of histamine and or products of arachidonic acid metabolism. Most data were obtained in guinea pig systems 20 years ago. Such data support a model in which C5a-stimulated contraction of isolated tracheal strips was due, in part, to histamine release...

Introduction Complement And Cancer

Although complement provides a rapid and efficient mean to protect the host from invasive microorganisms (for review see Walport, 2001a, b) its role in anti-cancer immune response remains vague and has even been questioned. Treatment of cancer patients with microbial vaccines, dating back to the 19th century, was attempted in a hope to stimulate the immune system to arrest the malignant process. The anti-cancer effect of Corynebacterium parvum and Staphylococcus aureus protein A could be...

Role of Complement in Allergy

Lilian Varga, Henriette Farkas and George Fust Third Department of Internal Medicine and Angoedema and Allergy Center, Semmelweis University, Budapest, Hungary Abstract For several decades the role for complement as a mediator of type I hypersensitivity reaction was not considered important. In the last ten years, however, the role of complement in allergy and asthma has been revisited and revised. This chapter summarizes the recent results on this topic. In in vitro and animal experiments...

C1 Inhibitor Deficiency and Systemic Lupus Erythematosus

Genetic and acquired forms of C1-INH are associated with the syndrome of hereditary angioneurotic edema, which consists of recurrent bouts of noninflammatory swelling involving the subcutaneous tissues, intestinal walls, airways, and lungs. Twice as many males as females are affected. Two major types of the genetic deficiency exist. In approximately 85 of patients, functional and antigenic assays show low serum concentration of the inhibitor. In the variant form, which comprises approximately...

Pathophysiology Of Mods

In critically ill patients (especially in patients with multiple-injury or after major surgery) there is a complex immune-modulation, usually with coexistence of pro-inflammatory events for host defenses and anti-inflammatory events in order to contain harmful effects of these inflammatory responses. It is now commonly understood that the development of MODS occurs mainly based on the following pathophysiologic sequel (1,15) (Figure 1). Figure 1. Pathophysiology of multi-organ dysfunction...

Neurologic and Neuromuscular Diseases

MAC has been implicated in the progression of lesions in patients with multiple sclerosis, Alzheimer's disease and neurotrauma. Increased levels of TCC are detected in the cerebrospinal fluid of patients with multiple sclerosis (Mollnes, 1987) and they seem to be higher in patients with multiple attacks (Sellebjerg, 1998) with a positive correlation between levels of TCC in the cerebrospinal fluid and neurological disability. TCC is deposited at the site of the lesion in the periventricular...

References Of Complement System

Ambrus, G., Gal, P., Kojima, M., Szilagyi, K., Balczer, J., Antal, J., Graf, L., Laich, A., Moffatt, B.E., Schwaeble, W., Sim, R.B., Zavodszky, P. Natural Substrates and Inhibitors of Mannan-Binding Lectin-Associated Serine Protease-1 and -2 A Study on Recombinant Catalytic Fragments. J Immunol 2003 170 1374-1382 Arlaud, G.J., Colomb, M.G., Gagnon, J. A functional model of the human C1 complex. Immun. Today 1987 8 106-116. Arlaud, G.J., Gaboriaud, C., Thielens, N.M., Rossi, V., Bersch, B.,...

Transplantation Of Nonvascular Grafts

Complement activation is usually not a problem in transplantation of autologous cells and tissues, like bone marrow cells, skin and bone. Allo-and xenotransplantation of skin and bone is usually intended for transient treatment, until the recipient's own tissue is regenerated. Strategies to avoid complement activation in these situations may not be crucial. Xeno-tissue used as bioscaffolds for remodelling seems to be relatively protected from rejection in contrast to whole organs (1). Cell...

Avoidance of Eradication

Once recognised by the host's complement system the invader has to introduce measures to avoid eradication by complement. This is achieved by removing (see 2.2.1), mimicking (2.2.2), or inhibiting (see 2.2.3) complement activation, or employing complement proteins via several highly sophisticated mechanisms (see 2.3.4). The principles are discussed and some representative examples are given below. A more detailed list of pathogens and their ways to avoid eradication by complement (19) and...

Complement and FcyR in experimental models of ICmediated disease

The Arthus reaction was first described almost 100 years ago by Maurice Arthus, who observed perivascular edema, infiltration of PMN and tissue damage following repeated injection of antigen intradermally (110). Today, the most commonly used experimental model is the reverse passive Arthus reaction. Preformed IgG antibodies are deposited in a desired tissue, followed by systemic application of the related antigen. Based on work in the 1960's and 1970's, it was understood that such induced...

Utilization of Membrane Complement Regulatory Proteins mCRP

Complement Regulatory Proteins

Like all normal cells, neoplastic cells are protected from autologous complement attack by several cell-surface complement inhibitors, such as CD35 (complement receptor type 1, CR1), CD55 (decay accelerating factor, DAF), CD46 (membrane cofactor protein, MCP) and CD59 (Protectin) (Morgan and Harris, 1999, chapters 7 and 8 in this volume). From numerous studies which have been performed in primary tumors and in tumor cell lines it is evident that almost all cancers studied express at least one...

Hypothesis on the Role of Complement Activation in type I Allergy Reactions

Results summarized in the chapter clearly indicate that allergens can activate the complement system both in RW-allergic and non-allergic individuals that is both in the absence and presence of IgE antibodies in the serum and or on the IgE-receptors of basophils, mast cells and other cell types. According to this hypothesis summarized in Figure 4, there are several types of interactions between complement activation products and the IgE mediated type 1 hypersensitivity reaction....

Hereditary C3 C5 C6 C7 and C8 Deficiencies

The major disease association with homozygous deficiencies of components C3 through C8 is infection (Table 1) few cases of SLE and SLE-like disease are associated with deficiencies of these components. The relative infrequency of these associations may indicate that no causal relationship exists, although such a relationship cannot yet be excluded because of the small numbers of cases of each deficiency studied. Of 24 reported cases of homozygous C3 deficiency, three patients had SLE-like...

Atypical Cutaneous Lupus Erythematosus a Hallmark of Deficiencies of Early Complement Components

SLE associated with homozygous deficiency of the early components of complement was the first of the associations of early complement deficiency with lupus disease to be reported (13). A striking finding present in the first index case and subsequently confirmed was that some of the lupus disease in these patients, called atypical cutaneous lupus erythematosus for lack of a better term, differs from classic lupus in the following four ways 1) increased incidence of discoid skin lesions, 2) an...

Hereditary C2 Deficiency

C2 deficiency is the most common homozygous complement component deficiency. The prevalence of either of C4 null genes is higher but prevalence of complete C4 deficiency, inheritance of both null genes is not (see Chapter 4). Larger numbers of patients with C1 INH deficiency than homozygous C2 patients have been reported because the inheritance of CI INH deficiency autosomal dominant (Table 1). Homozygous C2 deficiency has an approximate prevalence of 1 20,000 in the western European Caucasian...

Hypocomplementemic Urticarial Vasculitis Syndrome

Hypocomplementemic cutaneous vasculitis is an acquired form of deficiency that leads to chronic decreases in complement components C1, C2, C4, and C3. The syndrome is now called hypocomplementemic urticarial vasculitis syndrome (HUVS) but in the past was identified as SLE-related syndrome, hypocomplementemic cutaneous vasculitis, chronic hypocomplementemic cutaneous vasculitis, or hypocomplementemic vasculitis urticaria syndrome. Patients with this syndrome have several distinct clinical...