Neoantigenic Group on Fc Fragments in Rheumatoid Arthritis Synovial Fluids

Kolb, Gerald; Eckle, Ilsebill; Heidtmann, H.-H.; Neurath, F; Havemann, K

doi:10.3109/03009748809096760

Cited by 8 publications

(5 citation statements)

References 11 publications

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“…5b) and TNFa ( fig. 5c) decreased significantly after 2 and 4 weeks of AAT Immunoglobulin G CF-related proteases were found to cleave IgG into two antigen-binding fragments (F(ab) 2 ) and crystallisable fragments (Fc) [23,25,26]. In sputum samples of the CF patients in the present study, IgG bands of 26 kDa, 32 kDa, 36 kDa, 43 kDa and 54 kDa were detected under reducing conditions ( fig.…”

Section: Study Population Deposition Modes and Safetymentioning

confidence: 69%

α₁-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

Griese¹,

Latzin²,

Kappler³

et al. 2006

Eur Respir J

185

139

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The airways of cystic fibrosis (CF) patients are characterised by neutrophils that release high amounts of elastase overwhelming the local antiprotease shield. Inhalation of a 1 -antitrypsin (AAT) may restore the protease-antiprotease balance and attenuate airway inflammation in CF airways. The aims of the present study were: 1) to assess the best deposition region for inhaled AAT by two different inhalation strategies; and 2) to examine the effect of 4 weeks of AAT inhalation on lung function, protease-antiprotease balance and airway inflammation in CF patients.In a prospective, randomised study, 52 CF patients received a daily deposition by inhalation of 25 mg AAT for 4 weeks targeting their peripheral or bronchial compartment. The levels of elastase activity, AAT, pro-inflammatory cytokines, neutrophils, immunoglobulin G fragments and the numbers of Pseudomonas aeruginosa were assessed in induced sputum before and after the inhalation period.Inhalation of AAT increased AAT levels and decreased the levels of elastase activity, neutrophils, pro-inflammatory cytokines and the numbers of P. aeruginosa. However, it had no effect on lung function. No difference was found between the peripheral and bronchial inhalation mode.In conclusion, although no effect on lung function was observed, the clear reduction of airway inflammation after a 1 -antitrypsin treatment may precede pulmonary structural changes. The a 1 -antitrypsin deposition region may play a minor role for a 1 -antitrypsin inhalation in cystic fibrosis patients.

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Section: Study Population Deposition Modes and Safetymentioning

confidence: 69%

α₁-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

Griese¹,

Latzin²,

Kappler³

et al. 2006

Eur Respir J

185

139

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“…Release of human granulocyte elastase in inHatnmation can result in destruction of host proleins. This was demonstrated by the detection ofelastase speciiic IgG fragments in inflammatory Joint effusions [5], Elastase splits IgG in papain type Fc and Fab fragments which, however, have different tnolar ma.sses and isoelectric points [6|. The elastasc-induced Fc and Fab fragments influence the oxidative burst and enzyme release of granulocytes in vitro (6.…”

Section: Discussionmentioning

confidence: 99%

“…And some inhibitors of proteinkinase C are already described as acting as inhibitors of neutrophil chemotaxis [26. 28], Elastase-produced IgG fragments have been detected in vivo [5] and. therefore, the cflccts on leucocyte function were tested.…”

Section: Discussionmentioning

confidence: 99%

“…Chemotaxis (CT) of the activated neutrophils to the place of inflammation is the first step to destruction of invading mieroorganisms. At the inflammatory locus produciion ofactiviited oxygen radicals [lj and release oriysosomal enzymes [2] leads to destruction of foreign material hut also resulls in degradation or host proleins [3.4], Immunoglobulin G is produeed LU the plaee of inflammation and is split in vivo by neulrophil elastase (5].…”

Section: Inhibition Of Neutrophil Chemotaxis Bymentioning

confidence: 99%

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Inhibition of Neutrophil Chemotaxis by Elastase‐Generated IgG Fragments

1991

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IgG1 is cleaved in vitro by granulocyte elastase into Fc and Fab fragments. The elastase-specific Fc fragment has been previously detected in vivo. Biological activity of the fragments has been described in modulating neutrophil oxidative metabolism and enzyme release. To investigate further effects granulocyte chemotaxis (CT) was tested. The CT was assayed in Boyden chambers and the chemotactic index (CI) was calculated which represents the mean distance travelled by the activated cells. Stimulation of leucocyte CT by casein, activated serum and FMLP gives maximal values of delta CI = 46.7, 26.4 and 7.2 microns, respectively. Native IgG1 and the elastase-produced IgG fragments do not stimulate leucocyte CT. FMLP-stimulated CT is specifically inhibited by the elastase-produced Fc fragments. Addition of 7 nmol Fc to stimulus concentrations of 16 to 125 nM FMLP results in total inhibition of chemotaxis demonstrated by CI values which are lower than those for unstimulated cells. The inhibition of CT is concentration dependent in the range of 2 to 7 nmol Fc/10(6) PMN. Number and affinity of FMLP receptors are not influenced by Fc fragments, so Fc binds neither to FMLP nor the FMLP receptor. CT stimulated by casein shows a large portion of chemokinesis. Only at suboptimal casein concentrations do Fc and IgG have an inhibitory effect on CT (0.63 mg casein/ml, 10 nmol peptide/10(6) PMN). C5a-stimulated CT is not influenced by IgG or IgG fragments which indicates that the samples are not cytotoxic. So the FMLP and casein-stimulated CT is specifically inhibited by the elastase-produced Fc fragments in a low concentration range.

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“…C3 has been shown to be sensitive to the proteolytic activity of elastase, thrombin, plasmin and other tissue proteinases as well as of bacterial proteinases [30,34±5]. The results of the two-dimensional immunoelectrophoresis of peritoneal exudates resembled those found in pleural empyema [36]. Splitting of IgG by elastase and bacterial proteinases in vitro has also been described [30] and elastase-speci®c IgG fragments have been detected in vivo in arthritic synovial¯uids [37].…”

Section: Destruction Of Opsoninsmentioning

confidence: 99%

Proteolytic destruction of functional proteins by phagocytes in human peritonitis

Jochum¹,

Billing²,

Fröhlich³

et al. 1999

Eur J Clin Investigation

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Higher values of extracellularly released phagocyte proteinases concomitant with lower opsonin activity in exudates from patients with persistent peritonitis can be taken as a further hint of the involvement of local proteolysis-induced pathomechanisms in the development of lethal multiple organ failure, which occurred more frequently in patients with persistent peritonitis (54%) than in those with acute peritonitis (27%).

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Neoantigenic Group on Fc Fragments in Rheumatoid Arthritis Synovial Fluids

Cited by 8 publications

References 11 publications

α₁-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

α₁-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

Inhibition of Neutrophil Chemotaxis by Elastase‐Generated IgG Fragments

Proteolytic destruction of functional proteins by phagocytes in human peritonitis

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Neoantigenic Group on Fc Fragments in Rheumatoid Arthritis Synovial Fluids

Cited by 8 publications

References 11 publications

α1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

α1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

Inhibition of Neutrophil Chemotaxis by Elastase‐Generated IgG Fragments

Proteolytic destruction of functional proteins by phagocytes in human peritonitis

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α₁-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

α₁-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients