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- Amara, Umme, et al.
(författare)
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Molecular Intercommunication between the Complement and Coagulation Systems
- 2010
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 185:9, s. 5628-5636
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Tidskriftsartikel (refereegranskat)abstract
- The complement system as well as the coagulation system has fundamental clinical implications in the context of life-threatening tissue injury and inflammation. Associations between both cascades have been proposed, but the precise molecular mechanisms remain unknown. The current study reports multiple links for various factors of the coagulation and fibrinolysis cascades with the central complement components C3 and C5 in vitro and ex vivo. Thrombin, human coagulation factors (F) XIa, Xa, and IXa, and plasmin were all found to effectively cleave C3 and C5. Mass spectrometric analyses identified the cleavage products as C3a and C5a, displaying identical molecular weights as the native anaphylatoxins C3a and C5a. Cleavage products also exhibited robust chemoattraction of human mast cells and neutrophils, respectively. Enzymatic activity for C3 cleavage by the investigated clotting and fibrinolysis factors is defined in the following order: FXa > plasmin > thrombin > FIXa > FXIa > control. Furthermore, FXa-induced cleavage of C3 was significantly suppressed in the presence of the selective FXa inhibitors fondaparinux and enoxaparin in a concentration-dependent manner. Addition of FXa to human serum or plasma activated complement ex vivo, represented by the generation of C3a, C5a, and the terminal complement complex, and decreased complement hemolytic serum activity that defines exact serum concentration that results in complement-mediated lysis of 50% of sensitized sheep erythrocytes. Furthermore, in plasma from patients with multiple injuries (n = 12), a very early appearance and correlation of coagulation (thrombin-antithrombin complexes) and the complement activation product C5a was found. The present data suggest that coagulation/fibrinolysis proteases may act as natural C3 and C5 convertases, generating biologically active anaphylatoxins, linking both cascades via multiple direct interactions in terms of a complex serine protease system. The Journal of Immunology, 2010, 185: 5628-5636.
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| 2. |
- Burk, Anne-Maud, et al.
(författare)
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Early Complementopathy After Multiple Injuries in Humans.
- 2012
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Ingår i: Shock. - 1540-0514. ; 37:4, s. 348-354
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: After severe tissue injury, innate immunity mounts a robust systemic inflammatory response. However, little is known about the immediate impact of multiple trauma on early complement function in humans. In the present study we hypothesized that multiple trauma results in immediate activation, consumption and dysfunction of the complement cascade and that the resulting severe "complementopathy" may be associated with morbidity and mortality.Therefore a prospective multicenter study with 25 healthy volunteers and 40 polytrauma patients (mean injury severity score [ISS] = 30.3 ± 2.9) was performed. After polytrauma serum was collected as early as possible at the scene, upon admission to the emergency room and 4, 12, 24, 120 and 240 hours post trauma and analysed for the complement profile. Complement hemolytic activity (CH-50) was massively reduced within the first 24 h after injury, recovered only 5 days after trauma and discriminated between lethal and non-lethal 28-day outcome. Serum levels of the complement activation products C3a and C5a were significantly elevated throughout the entire observation period and correlatedwith the severity of traumatic brain injury and survival. The soluble terminal complement complex SC5b-9 and mannose-binding lectin (MBL) showed a biphasic response after trauma. Key fluid phase inhibitors of complement, such as C4b-binding protein (C4BP) and factor I, were significantly diminished early after trauma.The present data indicate an almost synchronically rapid activation and dysfunction of complement suggesting a trauma-induced "complementopathy" early after injury. These events may participate to the impairment of the innate immune response observed after severe trauma.
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| 3. |
- Matyschok, Jan, et al.
(författare)
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Compact, high-repetition-rate OPCPA system for high harmonic generation
- 2014
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Ingår i: Frontiers in Ultrafast Optics : Biomedical, Scientific, and Industrial Applications XIV - Biomedical, Scientific, and Industrial Applications XIV. - : SPIE. - 9780819498854 ; 8972
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Konferensbidrag (refereegranskat)abstract
- A compact, high-repetition rate optical parametric chirped pulse amplifier system emitting CEP-stable, few-cycle pulses with 10 μJ of pulse energy is reported for the purpose of high-order harmonic generation. The system is seeded from a commercially available, CEP-stabilized Ti:sapphire oscillator, delivering an octave-spanning spectrum from 600-1200 nm. The oscillator output serves on the one hand as broadband signal for the parametric amplification process and on the other hand as narrowband seed for an Ytterbium-based fiber preamplifier with subsequent main amplifiers and frequency doubling. Broadband parametric amplification up to 17 μJ at 200 kHz repetition rate was achieved in two 5 mm BBO crystals using non-collinear phase matching in the Poynting-vector-walk-off geometry. Efficient pulse compression down to 6.3 fs is achieved with chirped mirrors leading to a peak power exceeding 800 MW. We observed after warm-up time a stability of < 0.5 % rms over 100 min. Drifts of the CE-phase in the parametric amplifier part could be compensated by a slow feedback to the set point of the oscillator phase lock. The CEP stability was measured to be better than 80 mrad over 15 min (3 ms integration time). The experimentally observed output spectra and energies could be well reproduced by simulations of the parametric amplification process based on a (2+1)-dimensional nonlinear propagation code, providing important insight for future repetition rate scaling of OPCPA systems. The system is well-suited for attosecond science experiments which benefit from the high repetition rate. First results for high-order harmonic generation in argon will be presented.
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| 4. |
- Matyschok, Jan, et al.
(författare)
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Temporal and spatial effects inside a compact and CEP stabilized, few-cycle OPCPA system at high repetition rates
- 2013
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Ingår i: Optics Express. - 1094-4087. ; 21:24, s. 29656-29665
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Tidskriftsartikel (refereegranskat)abstract
- We present a compact and ultra-stable few-cycle OPCPA system. In two non-collinear parametric amplification stages pulse energies up to 17 mu J at 200 kHz repetition rate are obtained. Recompression of the broadband pulses down to 6.3 fs is performed with chirped mirrors leading to peak powers above 800 MW. The parametric amplification processes were studied in detail employing (2 + 1) dimensional numerical simulations and compared to experimental observations in terms of spectral shapes, pulse energy, spatial effects as well as delay dependent nonlinear mixing products. This gives new insights into the parametric process and design guidelines for high repetition rate OPCPA systems. (C) 2013 Optical Society of America
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