The complement system

The complement system consists of a tightly regulated network of proteins that play an important role in host defense and inflammation. Complement activation results in opsonization of pathogens and their removal by phagocytes, as well as cell lysis. Inappropriate complement activation and complement deficiencies are the underlying cause of the pathophysiology of many diseases such as systemic lupus erythematosus and asthma. This review represents an overview of the complement system in an effort to understand the beneficial as well as harmful roles it plays during inflammatory responses.

[1]  John D Lambris,et al.  Expression and Function of C5a Receptor in Mouse Microvascular Endothelial Cells1 , 2002, The Journal of Immunology.

[2]  M. Cicardi,et al.  C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. , 2009, Trends in molecular medicine.

[3]  R. Wetsel.  Expression of the complement C5a anaphylatoxin receptor (C5aR) on non-myeloid cells. , 1995, Immunology letters.

[4]  K. Kain,et al.  Complement driven innate immune response to malaria: fuelling severe malarial diseases , 2010, Cellular microbiology.

[5]  R. Karr,et al.  Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[6]  M. Walport.  Complement. First of two parts. , 2001, The New England journal of medicine.

[7]  John D Lambris,et al.  Complement-targeted therapeutics , 2007, Nature Biotechnology.

[8]  Samir N. Patel,et al.  C5 deficiency and C5a or C5aR blockade protects against cerebral malaria , 2008, The Journal of experimental medicine.

[9]  A. Valujskikh,et al.  Decay-accelerating factor modulates induction of T cell immunity , 2005, The Journal of experimental medicine.

[10]  H. Liebman,et al.  Thrombosis in patients with paroxysmal noctural hemoglobinuria is associated with markedly elevated plasma levels of leukocyte-derived tissue factor. , 2003, Thrombosis research.

[11]  M. Gershwin,et al.  Clinical Significance of Complement Deficiencies , 2009, Annals of the New York Academy of Sciences.

[12]  J. Krause,et al.  C5L2, a nonsignaling C5A binding protein. , 2003, Biochemistry.

[13]  M. Enomoto,et al.  A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells. , 2000, Molecular immunology.

[14]  G. Ingram,et al.  Complement in multiple sclerosis: its role in disease and potential as a biomarker , 2009, Clinical and experimental immunology.

[15]  P. Ward.  Sepsis, apoptosis and complement. , 2008, Biochemical pharmacology.

[16]  John D Lambris,et al.  Liver inflammation and regeneration: two distinct biological phenomena or parallel pathophysiologic processes? , 2006, Molecular immunology.

[17]  C. Garlanda,et al.  An integrated view of humoral innate immunity: pentraxins as a paradigm. , 2010, Annual review of immunology.

[18]  L. Fugger,et al.  Inherited deficiency of mannan-binding lectin-associated serine protease 2. , 2003, The New England journal of medicine.

[19]  M. Wills-Karp.  Complement activation pathways: a bridge between innate and adaptive immune responses in asthma. , 2007, Proceedings of the American Thoracic Society.

[20]  P. Ward,et al.  Complement in lung disease , 2006, Autoimmunity.

[21]  A. Blom,et al.  Complement activation and inhibition: a delicate balance. , 2009, Trends in immunology.

[22]  M. Lindberg,et al.  A second IgG-binding protein in Staphylococcus aureus. , 1998, Microbiology.

[23]  J. Lambris,et al.  Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis , 2010 .

[24]  B. Wąsowska.  Mechanisms involved in antibody- and complement-mediated allograft rejection , 2010, Immunologic research.

[25]  R. Abagyan,et al.  Defining the CD59-C9 binding interaction. , 2006, The Journal of biological chemistry.

[26]  S. Thiel,et al.  Mannan-binding-lectin-associated serine proteases, characteristics and disease associations , 2005, Springer Seminars in Immunopathology.

[27]  John D Lambris,et al.  Recent developments in low molecular weight complement inhibitors. , 2009, Molecular immunology.

[28]  P. Ward,et al.  Quantitative phagocytosis by neutrophils. II. Release of the C5-cleaving enzyme and inhibition of phagocytosis by rheumatoid factor. , 1973, Journal of immunology.

[29]  M. Carroll,et al.  The complement system in B cell regulation. , 2004, Molecular immunology.

[30]  A. Krarup,et al.  Role of early lectin pathway activation in the complement-mediated killing of Trypanosoma cruzi. , 2009, Molecular immunology.

[31]  Pedro Mejia,et al.  Biological activities of C1 inhibitor. , 2008, Molecular immunology.

[32]  G. Dubyak,et al.  Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. , 2008, Immunity.

[33]  M. Gawryl,et al.  Accentuated formation of the terminal C5b-9 complement complex in patient plasma precedes development of the adult respiratory distress syndrome. , 1988, The American review of respiratory disease.

[34]  B. Paul Morgan,et al.  Implication of Complement System and its Regulators in Alzheimer’s Disease , 2009, Current neuropharmacology.

[35]  A. Blom,et al.  Complement evasion strategies of pathogens-acquisition of inhibitors and beyond. , 2009, Molecular immunology.

[36]  J. V. van Strijp,et al.  Bacterial complement evasion. , 2007, Molecular immunology.

[37]  M. Frank,et al.  Therapeutic potential of complement modulation , 2010, Nature Reviews Drug Discovery.

[38]  R. Wallis.  Interactions between mannose-binding lectin and MASPs during complement activation by the lectin pathway , 2007, Immunobiology.

[39]  John D. Lambris,et al.  Complement evasion by human pathogens , 2008, Nature Reviews Microbiology.

[40]  J. V. Sarma,et al.  Functions of the complement components C3 and C5 during sepsis , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[41]  P. Monk,et al.  C5L2 Is a Functional Receptor for Acylation-stimulating Protein* , 2005, Journal of Biological Chemistry.

[42]  P. Heeger,et al.  Locally produced C5a binds to T cell-expressed C5aR to enhance effector T-cell expansion by limiting antigen-induced apoptosis. , 2008, Blood.

[43]  J. Younger,et al.  Generation of C5a by phagocytic cells. , 2002, The American journal of pathology.

[44]  John D Lambris,et al.  Generation of C5a in the absence of C3: a new complement activation pathway , 2006, Nature Medicine.

[45]  J. Köhl,et al.  The role of the anaphylatoxins in health and disease. , 2009, Molecular immunology.

[46]  D. Eisen.  Mannose-Binding Lectin Deficiency and Respiratory Tract Infection , 2009, Journal of Innate Immunity.

[47]  P. Monk,et al.  The human complement fragment receptor, C5L2, is a recycling decoy receptor , 2009, Molecular immunology.

[48]  C. Mackay,et al.  Functional roles for C5a receptors in sepsis , 2008, Nature Medicine.

[49]  P. Zipfel,et al.  Complement evasion of pathogens: common strategies are shared by diverse organisms. , 2007, Molecular immunology.

[50]  S. Thiel,et al.  Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms , 2007, Genes and Immunity.

[51]  P. Monk,et al.  The Orphan Receptor C5L2 Has High Affinity Binding Sites for Complement Fragments C5a and C5a des-Arg74 * , 2002, The Journal of Biological Chemistry.

[52]  D. Hourcade,et al.  Properdin: emerging roles of a pattern-recognition molecule. , 2010, Annual review of immunology.

[53]  Francesco Saverio Tedesco,et al.  Complement in human diseases: Lessons from complement deficiencies. , 2009, Molecular immunology.

[54]  H. Ploegh,et al.  Viral subversion of the immune system. , 2000, Annual review of immunology.

[55]  J. Atkinson,et al.  T-cell regulation: with complements from innate immunity , 2007, Nature Reviews Immunology.

[56]  V. Holers,et al.  Complement receptor 2, natural antibodies and innate immunity: Inter-relationships in B cell selection and activation. , 2007, Molecular immunology.

[57]  Wen-chao Song,et al.  Complement and its role in innate and adaptive immune responses , 2010, Cell Research.

[58]  Peter A. Ward,et al.  Harmful molecular mechanisms in sepsis , 2008, Nature Reviews Immunology.

[59]  J. Inal,et al.  A Schistosoma protein, Sh‐TOR, is a novel inhibitor of complement which binds human C2 , 2000, FEBS letters.

[60]  P. Ward,et al.  Expression and Function of the C5a Receptor in Rat Alveolar Epithelial Cells1 , 2002, The Journal of Immunology.

[61]  Peter A. Ward,et al.  Role of C5a–C5aR Interaction in Sepsis , 2004, Shock.