The membrane attack complex of complement (MAC) can induce reversible changes in cell membrane permeability resulting in significant but transient intracellular ionic changes in the absence of cell lysis. Because ion fluxes and cytosolic ionic changes are integral steps in the signaling cascade initiated when growth factors bind to their receptors, we hypothesized that the MAC-induced reversible changes in membrane permeability could stimulate cell proliferation. Using purified terminal complement components we have documented a mitogenic effect of the MAC for quiescent murine 3T3 cells. The MAC enhances the mitogenic effects of serum and PDGF, and also stimulates cell proliferation in the absence of other exogenous growth factors. MAC-induced mitogenesis represents a novel effect of the terminal complement complex that could contribute to focal tissue repair or pathological cell proliferation locally at sites of complement activation.
J A Halperin, A Taratuska, A Nicholson-Weller
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Enhanced complement activation and MAC formation accelerates severe COVID-19.
Ellsworth CR, Chen Z, Xiao MT, Qian C, Wang C, Khatun MS, Liu S, Islamuddin M, Maness NJ, Halperin JA, Blair RV, Kolls JK, Tomlinson S, Qin X |
Cellular and molecular life sciences : CMLS | 2024 |
Modulating acrylic acid content of nanogels for drug delivery & biocompatibility studies
A Sharma, K Raghunathan, H Solhaug, J Antony, J Stenvik, AM Nilsen, MA Einarsrud, S Bandyopadhyay |
Journal of Colloid and Interface Science | 2022 |
C3 Drives Inflammatory Skin Carcinogenesis Independently of C5
WD Jackson, A Gulino, L Fossati-Jimack, RC Seoane, K Tian, K Best, J Köhl, B Belmonte, J Strid, M Botto |
Journal of Investigative Dermatology | 2021 |
Challenges and approaches to studying pore-forming proteins
JT Benton, C Bayly-Jones |
Biochemical Society Transactions | 2021 |
Challenges and approaches to studying pore-forming proteins.
Benton JT, Bayly-Jones C |
Biochemical Society Transactions | 2021 |
Complement membrane attack complex: new roles, mechanisms of action, and therapeutic targets
CB Xie, D Jane-wit, JS Pober |
The American Journal of Pathology | 2020 |
Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition
C Huang, KP Fisher, SS Hammer, JV Busik |
International journal of molecular sciences | 2020 |
The role of complement membrane attack complex in dry and wet AMD - From hypothesis to clinical trials
R Kumar-Singh |
Experimental Eye Research | 2019 |
A distinctive histidine residue is essential for in vivo glycation-inactivation of human CD59 transgenically expressed in mice erythrocytes: Implications for human diabetes complications
R Sahoo, P Ghosh, M Chorev, JA Halperin |
American Journal of Hematology | 2017 |
The role of complement system in adipose tissue-related inflammation
SI Vlaicu, A Tatomir, D Boodhoo, S Vesa, PA Mircea, H Rus |
Immunologic Research | 2016 |
Increased Autoreactivity of the Complement-Activating Molecule Mannan-Binding Lectin in a Type 1 Diabetes Model
JA Østergaard, MM Ruseva, TH Malik, IT Hoffmann-Petersen, MC Pickering, S Thiel, TK Hansen |
Journal of Diabetes Research | 2016 |
Complement Membrane Attack and Tumorigenesis: A SYSTEMS BIOLOGY APPROACH
LD Towner, RA Wheat, TR Hughes, BP Morgan |
The Journal of biological chemistry | 2016 |
Retinal Pre-Conditioning by CD59a Knockout Protects against Light-Induced Photoreceptor Degeneration
D Song, B Wilson, L Zhao, R Bhuyan, M Bandyopadhyay, A Lyubarsky, C Yu, Y Li, L Kanu, T Miwa, WC Song, SC Finnemann, B Rohrer, JL Dunaief, AS Lewin |
PloS one | 2016 |
Ficolin B in Diabetic Kidney Disease in a Mouse Model of Type 1 Diabetes
CB Holt, JA Østergaard, E Axelgaard, GK Nielsen, Y Endo, S Thiel, TK Hansen |
Mediators of Inflammation | 2015 |
Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study
JA Østergaard, S Thiel, M Lajer, R Steffensen, HH Parving, A Flyvbjerg, P Rossing, L Tarnow, TK Hansen |
Diabetes care | 2015 |
Adenovirus-mediated delivery of Factor H attenuates complement C3 induced pathology in the murine retina: a potential gene therapy for age-related macular degeneration: Factor H rescue of C3-induced AMD model
SM Cashman, J Gracias, M Adhi, R Kumar-Singh |
The Journal of Gene Medicine | 2015 |
Exploitation of the Complement System by Oncogenic Kaposi's Sarcoma-Associated Herpesvirus for Cell Survival and Persistent Infection
MS Lee, T Jones, DY Song, JH Jang, JU Jung, SJ Gao, AV Moses |
PLoS pathogens | 2014 |
AAV-mediated expression of human PRELP inhibits complement activation, choroidal neovascularization and deposition of membrane attack complex in mice
MT Birke, E Lipo, M Adhi, K Birke, R Kumar-Singh |
Gene Therapy | 2014 |
Association of the pattern recognition molecule H-ficolin with incident microalbuminuria in an inception cohort of newly diagnosed type 1 diabetic patients: an 18 year follow-up study
JA Østergaard, S Thiel, P Hovind, CB Holt, HH Parving, A Flyvbjerg, P Rossing, TK Hansen |
Diabetologia | 2014 |
Early onset and enhanced growth of autochthonous mammary carcinomas in C3-deficient Her2/neu transgenic mice
S Bandini, C Curcio, M Macagno, E Quaglino, M Arigoni, S Lanzardo, A Hysi, G Barutello, L Consolino, DL Longo, P Musiani, G Forni, M Iezzi, F Cavallo |
OncoImmunology | 2013 |
Aurintricarboxylic acid inhibits complement activation, membrane attack complex, and choroidal neovascularization in a model of macular degeneration
E Lipo, SM Cashman, R Kumar-Singh |
Investigative ophthalmology & visual science | 2013 |
Topical Application of PPADS Inhibits Complement Activation and Choroidal Neovascularization in a Model of Age-Related Macular Degeneration
K Birke, E Lipo, MT Birke, R Kumar-Singh, ME Hartnett |
PloS one | 2013 |
Accelerated tumor growth mediated by sublytic levels of antibody-induced complement activation is associated with activation of the PI3K/AKT survival pathway
X Wu, G Ragupathi, K Panageas, F Hong, PO Livingston |
Clinical cancer research | 2013 |
Aurintricarboxylic Acid Inhibits Complement Activation, Membrane Attack Complex, and Choroidal Neovascularization in a Model of Macular Degeneration
E Lipo, SM Cashman, R Kumar-Singh |
Investigative ophthalmology & visual science | 2013 |
Accelerated Tumor Growth Mediated by Sub-lytic Levels of Antibody-Induced Complement Activation is Associated with Activation of the PI3K/AKT Survival Pathway
X Wu, G Ragupathi, K Panageas, F Hong, PO Livingston |
Clinical cancer research | 2013 |
Bioinformatic analysis of the membrane cofactor protein CD46 and microRNA expression in hepatocellular carcinoma
Z Lu, C Zhang, J Cui, QI SONG, L Wang, J Kang, P Li, X Hu, H Song, J Yang, Y Sun |
Oncology reports | 2013 |
Liver Regeneration
YA Nevzorova, C Trautwein |
Zakim and Boyer s Hepatology | 2012 |
Complement in Glomerular Disease
KA Vernon, HT Cook |
Advances in Chronic Kidney Disease | 2012 |
Membrane attack by complement: the assembly and biology of terminal complement complexes
CA Tegla, C Cudrici, S Patel, R Trippe, V Rus, F Niculescu, H Rus |
Immunologic Research | 2011 |
Complement in atherosclerosis: friend or foe?
WS Speidl, SP Kastl, K Huber, J Wojta |
Journal of Thrombosis and Haemostasis | 2011 |
Complement in Cancer and Cancer Immunotherapy
M Kolev, L Towner, R Donev |
Archivum Immunologiae et Therapiae Experimentalis | 2011 |
A Non Membrane-Targeted Human Soluble CD59 Attenuates Choroidal Neovascularization in a Model of Age Related Macular Degeneration
SM Cashman, K Ramo, R Kumar-Singh, A Fusco |
PloS one | 2011 |
Polyethylene Glycol (PEG)-induced Mouse Model of Choroidal Neovascularization
VV Lyzogubov, RG Tytarenko, J Liu, NS Bora, PS Bora |
The Journal of biological chemistry | 2011 |
Decay accelerating factor (CD55)-mediated attenuation of complement: therapeutic implications for age-related macular degeneration
KN Ma, SM Cashman, JH Sweigard, R Kumar-Singh |
Investigative ophthalmology & visual science | 2010 |
Pentraxin 3 and complement cascade activation in the failure of arteriovenous fistula
G Castellano, AD Vittorio, G Dalfino, A Loverre, D Marrone, S Simone, FP Schena, G Pertosa, G Grandaliano |
Atherosclerosis | 2010 |
Recombinant Membrane-targeted Form of CD59 Inhibits the Growth of Choroidal Neovascular Complex in Mice
NS Bora, P Jha, VV Lyzogubov, S Kaliappan, J Liu, RG Tytarenko, DA Fraser, BP Morgan, PS Bora |
The Journal of biological chemistry | 2010 |
Complement regulator CD59 protects against atherosclerosis by restricting the formation of complement membrane attack complex
G Wu, W Hu, A Shahsafaei, W Song, M Dobarro, GK Sukhova, RR Bronson, GP Shi, RP Rother, JA Halperin, X Qin |
Circulation research | 2009 |
CD59 but not DAF deficiency accelerates atherosclerosis in female ApoE knockout mice
G An, T Miwa, WL Song, JA Lawson, DJ Rader, Y Zhang, WC Song |
Molecular Immunology | 2009 |
Generation and phenotyping of mCd59a and mCd59b double-knockout mice
X Qin, W Hu, W Song, L Grubissich, X Hu, G Wu, S Ferris, M Dobarro, JA Halperin |
American Journal of Hematology | 2009 |
Do Archaea and bacteria co-infection have a role in the pathogenesis of chronic chagasic cardiopathy?
ML Higuchi, J Kawakami, R Ikegami, MB Clementino, FM Kawamoto, MM Reis, E Bocchi |
Memórias do Instituto Oswaldo Cruz | 2009 |
Complement C5 regulates the expression of insulin-like growth factor binding proteins in chronic experimental allergic encephalomyelitis
C Cudrici, T Ito, E Zafranskaia, S Weerth, V Rus, H Chen, F Niculescu, K Soloviova, C Tegla, A Gherman, CS Raine, ML Shin, H Rus |
Journal of Neuroimmunology | 2008 |
Current Topics in Complement II
JD Lambris |
2008 | |
Hypothesis: human serum-borne albumin bound lipids promote cellular survival after apoptosis induction by a variety of stimuli
M Schiller, S Franz, P Heyder, RE Voll, US Gaipl, HM Lorenz, JR Kalden, M Herrmann |
Apoptosis | 2007 |
CD59, a Complement Regulatory Protein, Controls Choroidal Neovascularization in a Mouse Model of Wet-Type Age-Related Macular Degeneration
NS Bora, S Kaliappan, P Jha, Q Xu, B Sivasankar, CL Harris, BP Morgan, PS Bora |
Journal of immunology (Baltimore, Md. : 1950) | 2007 |
Cross-talk between the complement system and endothelial cells in physiologic conditions and in vascular diseases
F Fischetti, F Tedesco |
Autoimmunity | 2006 |
Complement activation in diabetic ketoacidosis brains
WH Hoffman, CD Cudrici, E Zafranskaia, H Rus |
Experimental and Molecular Pathology | 2006 |
Role of complement and complement membrane attack complex in laser-induced choroidal neovascularization
PS Bora, JH Sohn, JM Cruz, P Jha, H Nishihori, Y Wang, S Kaliappan, HJ Kaplan, NS Bora |
Journal of immunology (Baltimore, Md. : 1950) | 2005 |
The Role of C5b-9 Terminal Complement Complex in Activation of the Cell Cycle and Transcription
M Fosbrink, F Niculescu, H Rus |
Immunologic Research | 2005 |
Emission of membrane vesicles: roles in complement resistance, immunity and cancer
D Pilzer, O Gasser, O Moskovich, JA Schifferli, Z Fishelson |
Springer Seminars in Immunopathology | 2005 |
Intrinsic resistance of hepatocytes to complement-mediated injury
CA Koch, A Kanazawa, R Nishitai, BE Knudsen, K Ogata, TB Plummer, K Butters, JL Platt |
Journal of immunology (Baltimore, Md. : 1950) | 2005 |
C5b-9 regulates peritubular myofibroblast accumulation in experimental focal segmental glomerulosclerosis
GK Rangan, JW Pippin, WG Couser |
Kidney International | 2004 |
The Role of Complement Activation in Atherosclerosis
F Niculescu, H Rus |
Immunologic Research | 2004 |
Molecular biology of cervical myelopathy and spinal cord injury: role of oligodendrocyte apoptosis
DH Kim, AR Vaccaro, FC Henderson, EC Benzel |
The Spine Journal | 2003 |
Sublytic terminal complement attack induces c-fos transcriptional activation in myotubes
TD Badea, JH Park, L Soane, T Niculescu, F Niculescu, H Rus, ML Shin |
Journal of Neuroimmunology | 2003 |
Deficiency of the Mouse Complement Regulatory Protein mCd59b Results in Spontaneous Hemolytic Anemia with Platelet Activation and Progressive Male Infertility
X Qin, N Krumrei, L Grubissich, M Dobarro, H Aktas, G Perez, JA Halperin |
Immunity | 2003 |
Calreticulin Is at the Surface of Circulating Neutrophils and Uses CD59 as an Adaptor Molecule
I Ghiran, LB Klickstein, A Nicholson-Weller |
The Journal of biological chemistry | 2003 |
Paroxysmal Nocturnal Hemoglobinuria and Related Disorders
M Omine, T Kinoshita |
2003 | |
Expression of Complement 3 and Complement 5 in Newt Limb and Lens Regeneration
Y Kimura, M Madhavan, MK Call, W Santiago, PA Tsonis, JD Lambris, KD Rio-Tsonis |
Journal of immunology (Baltimore, Md. : 1950) | 2003 |
Complement: Structure, Functions, Evolution, and Viral Molecular Mimicry
D Mastellos, D Morikis, SN Isaacs, MC Holland, CW Strey, JD Lambris |
Immunologic Research | 2003 |
Complement: more than a ‘guard’ against invading pathogens?
D Mastellos, JD Lambris |
Trends in Immunology | 2002 |
Complement C5b-9 Membrane Attack Complex Increases Expression of Endoplasmic Reticulum Stress Proteins in Glomerular Epithelial Cells
AV Cybulsky, T Takano, J Papillon, A Khadir, J Liu, H Peng |
The Journal of biological chemistry | 2002 |
Complement (C5b-9) induces DNA synthesis in rat mesangial cells in vitro
WG Couser, JW Pippin, SJ Shankland |
Kidney International | 2001 |
Involvement of the ERK mitogen-activated protein kinase in cell resistance to complement-mediated lysis
S Kraus, R Seger, Z Fishelson |
Clinical & Experimental Immunology | 2001 |
Terminal complement proteins in mediating processes of accelerated graft arteriosclerosis in cardiac transplants
Z Qian, W Hu, J Liu, F Sanfilippo, R Hruban, WM Baldwin |
Transplantation Proceedings | 2001 |
RGC-32 Increases p34 CDC2 Kinase Activity and Entry of Aortic Smooth Muscle Cells into S-phase
T Badea, F Niculescu, L Soane, M Fosbrink, H Sorana, V Rus, ML Shin, H Rus |
The Journal of biological chemistry | 2001 |
ACCELERATED GRAFT ARTERIOSCLEROSIS IN CARDIAC TRANSPLANTS: Complement Activation Promotes Progression of Lesions from Medium to Large Arteries1
Z Qian, W Hu, J Liu, F Sanfilippo, RH Hruban, WM Baldwin |
Transplantation | 2001 |
Mechanisms of Signal Transduction Activated by Sublytic Assembly of Terminal Complement Complexes on Nucleated Cells
F Niculescu, H Rus |
Immunologic Research | 2001 |
Complement as a mediator of vascular inflammation and activation in allografts
WM Baldwin, Z Qian, H Ota, M Samaniego, B Wasowska, F Sanfilippo, RH Hruban |
The Journal of Heart and Lung Transplantation | 2000 |
Terminal complement complexes concomitantly stimulate proliferation and rescue of Schwann cells from apoptosis
SM Dashiell, H Rus, CL Koski |
Glia | 2000 |
Molecular basis for a link between complement and the vascular complications of diabetes
J Acosta, J Hettinga, R Flückiger, N Krumrei, A Goldfine, L Angarita, J Halperin |
Proceedings of the National Academy of Sciences | 2000 |
Protein Kinase Activation and Protein Phosphorylation in Naegleria fowleri Amebae in Response to Normal Human Serum
DM Chu, TJ Ferguson, F Marciano-Cabral |
The Journal of Eukaryotic Microbiology | 2000 |
Identification and functional characterization of a new gene encoding the mouse terminal complement inhibitor CD59
YM Qian, X Qin, T Miwa, X Sun, JA Halperin, WC Song |
Journal of immunology (Baltimore, Md. : 1950) | 2000 |
Complement as a mediator of allograft injury: an inflammatory view
WM Baldwin, M Samaniego, Z Qian, H Ota, BA Wasowska, F Sanfilippo, RH Hruban |
Transplantation Reviews | 2000 |
Complement activation and atherosclerosis
F Niculescu, H Rus |
Molecular Immunology | 1999 |
Complement C5b-9 Induces Receptor Tyrosine Kinase Transactivation in Glomerular Epithelial Cells
AV Cybulsky, T Takano, J Papillon, AJ McTavish |
The American Journal of Pathology | 1999 |
COMPLEMENT CAUSES ALLOGRAFT INJURY BY CELL ACTIVATION RATHER THAN LYSIS:
WM Baldwin, Z Qian, B Wasowska, F Sanfilippo |
Transplantation | 1999 |
Complement activates phospholipases and protein kinases in glomerular epithelial cells
AV Cybulsky, J Papillon, AJ McTavish |
Kidney International | 1998 |
Depletion of intracellular Ca2+ stores, phosphorylation of eIF2alpha, and sustained inhibition of translation initiation mediate the anticancer effects of clotrimazole
H Aktas, R Flückiger, JA Acosta, JM Savage, SS Palakurthi, JA Halperin |
Proceedings of the National Academy of Sciences | 1998 |
Depletion of intracellular Ca2+ stores, phosphorylation of eIF2 , and sustained inhibition of translation initiation mediate the anticancer effects of clotrimazole
H Aktas, R Fluckiger, JA Acosta, JM Savage, SS Palakurthi, JA Halperin |
Proceedings of the National Academy of Sciences | 1998 |
The Human Complement System in Health and Disease
J Ahearn, A Rosengard |
The Human Complement System in Health and Disease | 1998 |
Terminal complement complexes induce cell cycle entry in oligodendrocytes through mitogen activated protein kinase pathway
H Rus, F Niculescu, T Badea, M L Shin |
Immunopharmacology | 1998 |
Molecular Cloning and Characterization of RGC-32 , a Novel Gene Induced by Complement Activation in Oligodendrocytes
TC Badea, FI Niculescu, L Soane, ML Shin, H Rus |
The Journal of biological chemistry | 1998 |
Textbook of Coronary Thrombosis and Thrombolysis
RC Becker |
1997 | |
Role of the complement membrane attack complex (C5b-9) in mediating experimental mesangioproliferative glomerulonephritis
J Brandt, J Pippin, M Schulze, GM Hänsch, CE Alpers, RJ Johnson, K Gordon, WG Couser |
Kidney International | 1996 |
Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall
HG Rus, R Vlaicu, F Niculescu |
Atherosclerosis | 1996 |
The transient pore formed by homologous terminal complement complexes functions as a bidirectional route for the transport of autocrine and paracrine signals across human cell membranes
JA Acosta, LR Benzaquen, DJ Goldstein, MT Tosteson, JA Halperin |
Molecular Medicine | 1996 |
Progressive renal failure--inability of podocytes to replicate and the consequences for development of glomerulosclerosis
J Floege, RJ Johnson, CE Alpers, S Fatemi-Nainie, CA Richardson, K Gordon, WG Couser |
Nephrology Dialysis Transplantation | 1996 |
Progressive renal failure--inability of podocytes to replicate and the consequences for development of glomerulosclerosis
J Floege, RJ Johnson, CE Alpers, S Fatemi-Nainie, CA Richardson, K Gordon, WG Couser |
Nephrology Dialysis Transplantation | 1996 |
Clotrimazole inhibits cell proliferation in vitro and in vivo
LR Benzaquen, C Brugnara, HR Byers, S Gattoni-Celli, JA Halperin |
Nature Medicine | 1995 |
Transient perturbation of endothelial integrity induced by natural antibodies and complement
S Saadi, JL Platt |
Journal of Experimental Medicine | 1995 |
Vascular Endothelium
MA Gimbrone, MI Cybulsky, N Kume, T Collins, N Resnick |
Annals of the New York Academy of Sciences | 1994 |
Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells
LR Benzaquen, A Nicholson-Weller, JA Halperin |
Journal of Experimental Medicine | 1994 |
Mechanisms of Progressive Renal Disease in Glomerulonephritis
WG Couser, RJ Johnson |
American Journal of Kidney Diseases | 1994 |
Receptor-independent activation of guanine nucleotide-binding regulatory proteins by terminal complement complexes
F Niculescu, H Rus, ML Shin |
The Journal of biological chemistry | 1994 |
Membrane signaling by complement C5b-9, the membrane attack complex
A Nicholson-Weller, JA Halperin |
Immunologic Research | 1993 |
The Complement System
A Agostoni, M Cicardi, M Gardinali, L Bergamaschini |
International journal of immunopathology and pharmacology | 1992 |