Blood-feeding insects inject potent salivary components including complement inhibitors into their host's skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the same chromatographic properties as the Lu. longipalpis salivary gland homogenate (SGH)counterparts and anti-rSALO antibodies blocked the classical pathway complement activity of rSALO and SGH. Both rSALO and SGH inhibited C4b deposition and cleavage of C4. rSALO, however, did not inhibit the protease activity of C1s nor the enzymatic activity of factor Xa, uPA, thrombin, kallikrein, trypsin and plasmin. Importantly, rSALO did not inhibit the alternative or the lectin pathway of complement. In conclusion our data shows that SALO is a specific classical pathway complement inhibitor present in the saliva of Lu. longipalpis. Importantly, due to its small size and specificity, SALO may offer a therapeutic alternative for complement classical pathway-mediated pathogenic effects in human diseases.
- MeSH
- Complement Activation drug effects MeSH
- Insect Proteins pharmacology MeSH
- Complement Inactivating Agents pharmacology MeSH
- Complement Pathway, Classical drug effects MeSH
- Complement C4 antagonists & inhibitors immunology metabolism MeSH
- Complement C1 antagonists & inhibitors immunology metabolism MeSH
- Humans MeSH
- Psychodidae immunology metabolism MeSH
- Recombinant Proteins pharmacology MeSH
- Saliva metabolism MeSH
- Chromatography, High Pressure Liquid MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
The complement system is a major part of the innate immunity. The first component of the classical pathway of complement activation, C1q, plays a crucial role in the clearance of immune complexes and apoptotic bodies from the organism. Autoantibodies against C1q (anti-C1q) have been found in a number of autoimmune and infectious diseases. They have been best described in patients with systemic lupus erythematosus, where they are thought to play a pathogenic role in lupus nephritis (LN). Their high negative predictive value for the occurrence of active proliferative LN, as well as their possible ability to indicate a renal flare as soon as 6 months in advance, have rendered anti-C1q antibodies a novel non-invasive tool in the detection of active LN.
- MeSH
- Apoptosis immunology MeSH
- Autoantibodies blood MeSH
- Biomarkers blood MeSH
- Financing, Organized MeSH
- Antigen-Antibody Complex immunology MeSH
- Complement Pathway, Classical MeSH
- Complement C1q immunology MeSH
- Humans MeSH
- Lupus Nephritis diagnosis immunology MeSH
- Immunity, Innate MeSH
- Disease Progression MeSH
- Lupus Erythematosus, Systemic immunology blood MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
Komplementový systém je důležitou součástí vrozené imunity. Ačkoli u systémových autoimunitních chorob je jeho účinek spíše protektivní, při autoimunitních zánětech štítné žlázy aktivně napadá tyreocyty, které exprimují řadu složek komplementu a komplementových inhibitorů. Aktivace klasické cesty komplementu je ve tkáni štítné žlázy započata buď protilátkami proti antigenům štítné žlázy ve formě imunokomplexů, nebo vazbou složky komplementu C4 na tyreoidální peroxidázu, anebo přímou aktivací reaktivními kyslíkovými radikály. Tyreocyty jsou proti útoku komplementu rezistentní; při napadení však uvolňují prozánětlivé cytokiny a reaktivní kyslíkové radikály, vedoucí k progresi zánětu. Klinický význam komplementu u autoimunitních zánětů štítné žlázy byl dosud sledován pouze u poporodní tyreoiditidy. Přes jistý pokrok však zůstává role komplementového systému v etiopatogenezi autoimunitních procesů málo poznána.
The complement system is a crucial part of the innate immune system. In systemic autoimmune disorders, its effects tend to be protective. On the contrary, in the autoimmune thyroid disorders (AIT) the complement actively attacks thyrocytes, which express a number of complement components as well as complement inhibitory molecules. According to the experimental studies different ways of complement activation might occur in the thyroid tissue. All ensue via the classical pathway that is started either by immune complexes containing complement activating autoantibodies against thyroid autoantigens, or by direct binding of C4 to the molecule of thyroid peroxidase (TPO); or by direct complement activation by reactive oxygen radicals. Thyrocytes are relatively resistant to the complement attack. However, sublethaly injured thyrocytes release proinflammatory cytokines and reactive oxygen radicals and thus promote the inflammatory process in the thyroid. So far, the clinical significance of the complement in the thyroid has been studied only in postpartum thyroiditis. The exact role of complement in the pathogenesis of AIT remains to be elucidated.
[Long pentraxin PTX3 - a new acute phase reactant]
Pentraxin 3 je nově objeveným proteinem akutní fáze, který sdílí částečnou podobu se známým pentraxi-nem C-reaktivním proteinem. Zatímco v průběhu reakce akutní fáze je CRP vytvářen v játrech a působí na úrovni celého organismu, PTX3 vzniká přímo v zánětlivém ložisku a jeho působení je lokalizované do postižené tkáně. Společnou vlastností obou pentraxinů je aktivace komplementu klasickou cestou. Oba pentraxiny se podílejí na patogenezi některých zánětlivých onemocnění s autoimunitní složkou. Z tohoto pohledu se největší zájem soustředí na aterosklerózu a její komplikace. V přehledovém článku jsou popsá¬ny účinky PTX3 v patogenezi revmatoidní artritidy, igA nefropatie a aterosklerózy. Je zdůrazněna pro¬gnostická výpovědní hodnota PTX3 u nemocných s akutním infarktem myokardu, nemocných v septickém šoku a nemocných s plicní tuberkulózou.
Pentraxin 3 is a novel protein of the acute phase response which shares a striking degree of homology with the well-known pentraxin C-reactive protein. Whereas CRP is made up in the liver and its effects are disse-minated systemically to the whole body, PTX3 is produced directly within the inflammatory focus and its effects are targeted to the inflamed tissue. Both pentraxins share the ability to activate complement via the classical pathway. Both PTX3 and CRP také part in the pathogenesis of some inflammatory diseases featu-ring an autoimmune component. In this respect, atherosclerosis including its complications represents a pa-thological condition that evokes much interest nowadays. This review article presents recently discovered effects of PTX3 in the pathogenesis of rheumatoid arthritis, the IgA nephropathy and atherosclerosis, with speciál emphasis being laid on the prognostic value of PTX3 in patients suffering from acute myocardial infaretion, septic shock and pulmonary form of tuberculosis.
- MeSH
- Arteriosclerosis physiopathology MeSH
- Autoimmune Diseases MeSH
- C-Reactive Protein analogs & derivatives diagnostic use adverse effects MeSH
- Research Support as Topic MeSH
- Glomerulonephritis, IGA physiopathology MeSH
- Myocardial Infarction MeSH
- Complement Pathway, Classical physiology immunology MeSH
- Humans MeSH
- Tuberculosis, Pulmonary MeSH
- Acute-Phase Proteins diagnostic use adverse effects MeSH
- Arthritis, Rheumatoid physiopathology MeSH
- Shock, Septic MeSH
- Check Tag
- Humans MeSH
- MeSH
- Allergy and Immunology MeSH
- Complement Pathway, Alternative * MeSH
- Adult MeSH
- Immunoglobulins MeSH
- Complement Pathway, Classical * MeSH
- Clinical Laboratory Techniques MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Nasal Polyps * diagnosis MeSH
- Aged MeSH
- Statistics as Topic MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
