Distinct Tissue Site-Specific Requirements of Mast Cells and Complement Components C3/C5a Receptor in IgG Immune Complex-Induced Injury of Skin and Lung

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by an almost daily recurrence of wheal and flare with itch for more than 6 weeks, in association with the release of stored inflammatory mediators, such as histamine, from skin mast cells and/or peripheral basophils. The involvement of the extrinsic coagulation cascade triggered by tissue factor (TF) and complement factors, such as C3a and C5a, has been implied in the pathogenesis of CSU. However, it has been unclear how the TF-triggered coagulation pathway and complement factors induce the activation of skin mast cells and peripheral basophils in patients with CSU. In this review, we focus on the role of vascular endothelial cells, leukocytes, extrinsic coagulation factors and complement components on TF-induced activation of skin mast cells and peripheral basophils followed by the edema formation clinically recognized as urticaria. These findings suggest that medications targeting activated coagulation factors and/or complement components may represent new and effective treatments for patients with severe and refractory CSU.

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Immune complexes: characteristics, clinical correlations, and interpretive approaches in the clinical laboratory.

Clinical Chemistry ◽

10.1093/clinchem/28.6.1259 ◽

1982 ◽

Vol 28 (6) ◽

pp. 1259-1271 ◽

Cited By ~ 25

Author(s):

S E Ritzmann ◽

J C Daniels

Keyword(s):

Immune Complex ◽

Lupus Erythematosus ◽

Immune Complexes ◽

Complex Disease ◽

Clinical Medicine ◽

Clinical Laboratory ◽

Therapeutic Monitoring ◽

Serum Samples ◽

Complement Components ◽

Antigen Antibody

Abstract Immune-complex-mediated injury is thought to play a role in diseases such as rheumatoid arthritis, systemic lupus erythematosus, serum sickness, various infectious diseases, and malignancies. With increased appreciation of the biological and pathological significance of circulating immune complexes has come efforts to develop appropriate techniques for identifying and measuring them. Common approaches exploit such phenomena as the attachment of complement components to antigen-antibody complexes, the presence of specialized receptors for immune complexes at the surface of cells, and the ability of rheumatoid factor to bind with immune complexes. This variety of assay systems for immune complexes has yielded abstruse results in numerous human pathological conditions. Unfortunately, these results seldom correlate with one another in a given disease. Thus, use of a panel of immune complex assays has been recommended. Indirect consequences of immune complex disease may still be appraised and evaluated with some confidence in clinical medicine: measurements of C3 and C4, cryoglobulins, serum viscosity, and turbidity of serum samples. Measurement of immune complexes may be useful in diagnosis, prognosis, and therapeutic monitoring, but it is the characterization of immune complexes that holds the greatest potential for better understanding of disease mechanisms.

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Functional Expression of the Novel C5a Receptor C5L2 in Human Mast Cells

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2012.12.1518 ◽

2013 ◽

Vol 131 (2) ◽

pp. AB239 ◽

Cited By ~ 1

Author(s):

Priyanka Pundir ◽

Marianna Kulka

Keyword(s):

Mast Cells ◽

Functional Expression ◽

The Novel ◽

C5a Receptor ◽

Human Mast Cells

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Impaired Inflammatory Responses in the Reverse Arthus Reaction Through Genetic Deletion of the C5a Receptor

Journal of Experimental Medicine ◽

10.1084/jem.186.5.749 ◽

1997 ◽

Vol 186 (5) ◽

pp. 749-756 ◽

Cited By ~ 145

Author(s):

Uta E. Höpken ◽

Bao Lu ◽

Norma P. Gerard ◽

Craig Gerard

Keyword(s):

Immune Complex ◽

Peritoneal Cavity ◽

Inflammatory Responses ◽

Dominant Role ◽

Neutrophil Migration ◽

Arthus Reaction ◽

Edema Formation ◽

C5a Receptor ◽

C5a Anaphylatoxin ◽

Deficient Mice

We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin receptor prevented lung injury in immune complex–mediated inflammation. In this study, we compare the effect of C5aR deficiency in immune complex–induced inflammation in the peritoneal cavity and skin with the results derived from our immune complex alveolitis model. C5aR- deficient mice exhibit decreased migration of neutrophils and decreased levels of TNF-α and interleukin 6 in the peritoneal reverse passive Arthus reaction compared to their wild-type littermates. In the reverse passive Arthus reaction in the skin the C5aR was also required for the full expression of neutrophil influx and edema formation; C5aR-deficient mice showed reduced neutrophil migration and microvascular permeability changes. In contrast to our studies in immune complex–induced lung inflammation, C5aR deficiency does not completely prevent injury in the peritoneal cavity and skin. These data indicate a dominant role for the C5aR and its ligand in the reverse passive Arthus reaction in the lung and a synergistic role together with other inflammatory mediators in immune complex–mediated peritonitis and skin injury.

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Expression of the C5a receptor (CD88) on synovial mast cells in patients with rheumatoid arthritis

Arthritis & Rheumatism ◽

10.1002/1529-0131(199802)41:2<233::aid-art7>3.0.co;2-v ◽

1998 ◽

Vol 41 (2) ◽

pp. 233-245 ◽

Cited By ~ 59

Author(s):

Hans P. Kiener ◽

Mehrdad Baghestanian ◽

Martin Dominkus ◽

Sabine Walchshofer ◽

Minoo Ghannadan ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mast Cells ◽

C5a Receptor

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Abrogation of immune complex glomerulonephritis by native carboxypeptidase and pharmacological antagonism of the C5a receptor

Cellular and Molecular Immunology ◽

10.1038/cmi.2015.45 ◽

2015 ◽

Vol 13 (5) ◽

pp. 651-657 ◽

Cited By ~ 4

Author(s):

Jessy J. Alexander ◽

Lee D. Chaves ◽

Anthony Chang ◽

Shruti Dighe ◽

Alexander Jacob ◽

...

Keyword(s):

Immune Complex ◽

C5a Receptor ◽

Immune Complex Glomerulonephritis

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The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration

Journal of Experimental Medicine ◽

10.1084/jem.20030374 ◽

2003 ◽

Vol 198 (6) ◽

pp. 913-923 ◽

Cited By ~ 282

Author(s):

Christoph W. Strey ◽

Maciej Markiewski ◽

Dimitrios Mastellos ◽

Ruxandra Tudoran ◽

Lynn A. Spruce ◽

...

Keyword(s):

Liver Regeneration ◽

Nuclear Factor Κb ◽

Hepatocyte Proliferation ◽

Complement Components ◽

C5a Receptor ◽

Proinflammatory Mediators ◽

Toxic Injury ◽

Hepatocyte Regeneration ◽

Impaired Liver ◽

Parenchymal Damage

Complement has been implicated in liver repair after toxic injury. Here, we demonstrate that complement components are essential for liver regeneration, and mediate their effect by interacting with key signaling networks that promote hepatocyte proliferation. C3- or C5-deficient mice exhibited high mortality, parenchymal damage, and impaired liver regeneration after partial hepatectomy. Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. Interception of C5a receptor signaling resulted in suppression of IL-6/TNFα induction and lack of C3 and C5a receptor stimulation attenuated nuclear factor–κB/STAT-3 activation after hepatectomy. These data indicate that C3a and C5a, two potent inflammatory mediators of the innate immune response, contribute essentially to the early priming stages of hepatocyte regeneration.

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Complement Synthesis in the Diseased Kidney and its Role in Renal Damage

Journal of Dhaka Medical College ◽

10.3329/jdmc.v20i1.8566 ◽

1970 ◽

Vol 20 (1) ◽

pp. 15-19

Author(s):

M Khatun ◽

ASM Nurunnabi ◽

S Ara ◽

M Rahman

Keyword(s):

Renal Biopsy ◽

Immune Complex ◽

Mesangial Cells ◽

Tissue Injury ◽

Armed Forces ◽

Military Hospital ◽

Direct Immunofluorescence ◽

Complement Components ◽

Medical University

Renal biopsy tissues were taken from 142 suspected glomerulonephritic patients who were admitted into the Department of Nephrology of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and Combined Military Hospital (CMH), Dhaka Cantonment, Dhaka. The tissues were processed for both Light Microscopy (LM) and Direct Immunofluorescence (DIF) studies. The study was done in the Department of Anatomy, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and Armed Forces Institute of Pathology (AFIP), Dhaka Cantonment, Dhaka, from March to December 1999. Seven histopathological types of glomerulonephritis were identified with LM and another one type i.e. IgA Nephropathy was identified exclusively by using DIF. Diffuse immunofluorescence positivity was found in 44.36% cases. C3 components were found in all cases irrespective of the histopathological type of glomerulonephritis. Immune complex deposits were observed in immunofluorescence both in the mesangium and the glomerular basement membrane (GBM) with more generalized and less scattered distributions. Immunoglobulins (Ig) were tested for IgG, IgA and IgM. IgG was found the most common (74.60%) among immune complex deposits. Notable LM features include proliferation of mesangial cells, expansion of mesangial matrix, thickening of GBM, infiltration of glomerular macrophages, platelets and neutrophil and crescent formation. The presence of IgG in the mesangium of the kidney of the glomerulonephritic patient suggests a role of IgG in the inflammatory process. There is also evidence that C3 is synthesized within the glomeruli of the patients with glomerulonephritis. Finding the role of the complement components in pathogenesis of glomerulonephritis, a keen observation is needed to determine the extent of local complement synthesis and their involvement in tissue injury process. Key words: Complement synthesis; immune complex; glomerulonephritis; renal biopsy. DOI: http://dx.doi.org/10.3329/jdmc.v20i1.8566 J Dhaka Med Coll. 2011; 20(1) : 15-19

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