Aprotinin® diminishes inflammatory processes

Soeparwata, Rasjid; Hartman, Alan R.; Frerichmann, U.; Stefano, George B.; Scheld, Hans H.; Bilfinger, Thomas V.

doi:10.1016/0167-5273(96)02573-9

Cited by 32 publications

(14 citation statements)

References 39 publications

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“…individ uals may be pro ne to a path ological response to CPS which could differ from the observed changes in the limited number of the investigated pat ients . The application of Apron mns as a partof our routi ne management of pat ients w ith cardiopulmo nary bypass may have reduced the immune respon se in the CPBgroup (20).…”

Section: Discussionmentioning

confidence: 99%

Changes of Leukocyte Subsets in Coronary Artery Bypass Surgery: Cardiopulmonary Bypass Versus ‘Off-pump’ techniques

Diegeler¹,

Tárnok²,

Rauch³

et al. 1998

Thorac cardiovasc Surg

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Section: Discussionmentioning

confidence: 99%

Changes of Leukocyte Subsets in Coronary Artery Bypass Surgery: Cardiopulmonary Bypass Versus ‘Off-pump’ techniques

Diegeler¹,

Tárnok²,

Rauch³

et al. 1998

Thorac cardiovasc Surg

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“…The well-established anti-inflammatory potential of aprotinin has been recently extended to the inhibition of cell activation and release of cytokines [29] and, with particularly relevance to our studies, to reduction of collagen degradation [19]. Nonetheless, aprotinin has not been demonstrated to significantly ameliorate the course of acute inflammatory conditions, such as pancreatitis or pneumonia, in vivo.…”

Section: Discussionmentioning

confidence: 93%

Mechanism of antinephritic effect of proteinase inhibitors in experimental anti-GBM glomerulopathy

Hruby¹,

Wendycz²,

Kopeć³

et al. 1999

Res. Exp. Med.

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We have previously documented amelioration of rat autologous anti-GBM nephritis with the antiproteolytic drugs epsilon-aminocaproic acid (EACA) and aprotinin, given from the day of induction or later in the course of disease. In the present study we investigated potential mechanisms of this effect by assessing interactions of the drugs with proteinase-dependent generation of superoxide anion in glomeruli, and their influence on both GBM degradation in vitro and activity of glomerular proteolytic enzymes. Release of O2- by enzymatically disrupted glomeruli, isolated from nephritic control or EACA/aprotinin-treated rats, was measured with the ferricytochrome reduction method and its activity was correlated with proteinuria and glomerular cellularity at the early phase of the disease. The hydroxyproline release assay was used to quantitate degradation of rat GBM in vitro by leukocyte proteinases stimulated by phorbol myristate acetate (PMA), in the presence or absence of EACA and aprotinin. Finally, the activities of elastase, cathepsins B and L, and plasmin, together with collagenase-like activity, were assessed fluorimetrically in homogenates of glomeruli isolated from control and antiproteolytic-drug-treated nephritic rats. EACA and aprotinin notably inhibited production of superoxide by nephritic glomeruli (by 47% and 66%, respectively), and this effect was not significantly correlated with proteinuria or glomerular hypercellularity at the early stage of disease. On the other hand, generation of O2- by glomeruli of untreated nephritic rats was notably correlated with total glomerular cell counts and numbers of macrophages infiltrating glomeruli. PMA-stimulated neutrophils and macrophages caused degradation of isolated rat GBM in vitro, markedly attenuated in the presence of EACA (P<0.0005) and, to a lesser extent, by addition of aprotinin (P<0.01). The activity of elastase was significantly reduced in glomeruli of nephritic rats treated with EACA or aprotinin (both P<0.001), while activities of remaining proteinases were not appreciably affected. The beneficial influence of proteinase inhibitors on rat anti-GBM disease may be due, at least in part, to abrogation of superoxide generation in nephritic glomeruli. EACA and aprotinin also have potential to interfere with digestion of GBM, and both these effects may be related to suppression of glomerular elastase.

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“…These mechanisms indicate the significance of various host processes and shed light on their vulnerable steps. These vulnerable points of alteration may be used in medicine to curtail these processes where deemed appropriate [12].…”

Section: Discussionmentioning

confidence: 99%

Amino‐acid‐sequence Determination and Biological Activity of Cytin, a Naturally Occurring Specific Chymotrypsin Inhibitor from the Leech Theromyzon tessulatum

Chopin

Bilfinger

Stefano

et al. 1997

European Journal of Biochemistry

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We purified a chymotrypsin inhibitor, designated cytin, from the rhynchobdellid leech Theromyzon tessulatum. This 7.4-kDa peptide was purified to apparent homogeneity by gel-permeation and anionexchange chromatographies, followed by reverse-phase HPLC. The structure of cytin was determined by reduction, S-p-pyridilethylation, automated Edman degradation, and electrospray mass spectrometry. Cytin is formed by the association of two protein chains, which are linked by a disulfide bridge. Chain A consists of 43 and chain B of 22 amino acid residues. Chain B exhibits 40-63% sequence similarity with the N-terminal sequences of subtilisinkhymotrypsin inhibitors isolated from barley seeds. Cytin inhibited chymotrypsin (K, 600 pM) and weakly inhibited trypsin (Kl 350 nM). This chymotrypsin inhibitor, in contrast to others isolated from leeches, does not inhibit elastase or cathepsin G. Furthermore, cytin (10 pM) significantly diminishes the level of human granulocyte and monocyte activation induced by lipopolysaccharide (1 U/ml) in a manner similar to that of aprotinin. These data indicate that this chymotrypsin inhibitor may be biomedically significant.

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Aprotinin® diminishes inflammatory processes

Cited by 32 publications

References 39 publications

Changes of Leukocyte Subsets in Coronary Artery Bypass Surgery: Cardiopulmonary Bypass Versus ‘Off-pump’ techniques

Changes of Leukocyte Subsets in Coronary Artery Bypass Surgery: Cardiopulmonary Bypass Versus ‘Off-pump’ techniques

Mechanism of antinephritic effect of proteinase inhibitors in experimental anti-GBM glomerulopathy

Amino‐acid‐sequence Determination and Biological Activity of Cytin, a Naturally Occurring Specific Chymotrypsin Inhibitor from the Leech Theromyzon tessulatum

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