Peptidase activities in serum and bronchoalveolar lavage fluid from allergic asthmatics — comparison with healthy non‐smokers and smokers and effects of inhaled glucocorticoids

Velden, van der; Naber, Brigitta A.E.; Hal, Van; Overbeek,; Hoogsteden,; Versnel,

doi:10.1046/j.1365-2222.1999.00550.x

Cited by 31 publications

(19 citation statements)

References 42 publications

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“…DPPIV activities reduced in smokers and increased in diabetics have already been reported. 11,12 This correlates with observations in patients receiving ACEI and raises the question of whether the higher frequency of smoking subjects developing ACEI-induced angioedema may be a consequence of DPPIV decrease. Thus, the role of SP may be more prominent than suspected previously.…”

Section: Dppiv Activity and Acei-induced Angioedemasupporting

confidence: 70%

Is Dipeptidylpeptidase IV the Missing Link in Angiotensin-Converting Enzyme Inhibitor–Induced Angioedema?

Grouzmann

Buclin

2008

Hypertension

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A pproximately 40 million people worldwide are currently treated with angiotensin-converting enzyme (ACE) inhibitors (ACEIs) for hypertension, congestive heart failure, coronary diseases, and diabetic nephropathy. The primary mechanism of action of ACEIs is blocking of the renin angiotensin system by inhibiting the conversion of angiotensin I to the vasoconstrictor angiotensin II. Few serious adverse events specific to ACE inhibition were initially reported, because they are actually rare. However, Յ0.68 of every 100 patients seem to experience angioedema with ACEI, sometimes months and even years after the start of medication. 1 The pathophysiology of ACEI-induced angioedema is presently thought to result from the role of ACE in the degradation of other peptides including bradykinin (BK) and substance P (SP The metabolism of BK and SP by proteases is redundant, with several enzymes available to terminate their biological action. Both ACE and neutral endopeptidase (NEP) play major roles in inactivating BK and SP. 2 BK is also processed by aminopeptidase P, but a contribution of this peptidase in angioedema during ACEI is unlikely, despite a downregulation of its activity reported in some cases. 4 BK is also a substrate of kininase I, capable of cleaving the last residue off its C-terminal end to generate des-Arg 9 -BK, a fragment without affinity for the B2 receptor but an agonist on the inducible B1 receptor expressed during inflammation. 4 On the other hand, SP is sequentially truncated by dipeptidylpeptidase IV (DP-PIV) into SP3-11 and then SP5-11, which is 1000-fold less potent than the native peptide. 5 However, the physiological importance of DPPIV in the inactivation of SP and the role of a reduction of DPPIV activity in ACEI-induced angioedema had not been evaluated before the article by Byrd et al,6 published in this issue of Hypertension. ACE Inhibition and AngioedemaThe incidence of ACEI-induced angioedema ranges from 0.1% in patients treated with short-acting drugs such as captopril to 0.68% in patients treated with more potent inhibitors such as enalapril, as reported in the Omapatrilat Cardiovascular Treatment Versus Enalapril Study. 7 Recently, dual vasopeptidase inhibition seemed very promising by blocking NEP, thereby increasing circulating concentrations of natriuretic peptides, and ACE, thus hampering angiotensin II generation. Omapatrilat was the first dual inhibitor in this new class of drugs that was highly active in hypertension. 7 Unfortunately, vasopeptidase inhibitors caused up to a 2.1% rate of angioedema after a short period of treatment. Interestingly, smoking was associated with an even higher 3.9% occurrence of angioedema in omapatrilat-treated patients. 7 In contrast, diabetic patients seem less prone to develop angioedema during ACE or ACE/NEP blockade. 5 In this context, the new drug application for omapatrilat has been withdrawn pending safety reassessment. The increased rate of angioedema induced by dual ACE/NEP inhibitors strengthens the hypothesis that BK and/or SP are invol...

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Section: Dppiv Activity and Acei-induced Angioedemasupporting

confidence: 70%

Is Dipeptidylpeptidase IV the Missing Link in Angiotensin-Converting Enzyme Inhibitor–Induced Angioedema?

Grouzmann

Buclin

2008

Hypertension

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“…Van der Velden and colleagues did not observe any differences in the peptidase activities between allergic asthmatics and healthy nonsmokers. Because the DP4-like activities in the BAL fluid and the lung might at least be partially released by activated CD4-positive T-cells (Juillerat-Jeanneret et al 1997), they explained their observations with an unaltered T-cell number in the allergic asthmatics (van der Velden et al 2000). Corresponding to the abovedocumented upregulated DP4-like activities in the lung and BAL fluid of rats after asthma induction, our previous studies showed an elevated number of activated T-cells after asthma induction in this rat model (Skripuletz et al 2007).…”

Section: The Journal Of Histochemistry and Cytochemistrymentioning

confidence: 78%

Regulation of Expression and Function of Dipeptidyl Peptidase 4 (DP4), DP8/9, and DP10 in Allergic Responses of the Lung in Rats

Stephan

Schmiedl

et al. 2007

J Histochem Cytochem.

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S U M M A R Y The expression of dipeptidyl peptidase 4 (DP4, CD26) affects T-cell recruitment to lungs in an experimental rat asthma model. Furthermore, the gene of the structural homologous DP10 represents a susceptibility locus for asthma in humans, and the functional homologous DP8/9 are expressed in human leukocytes. Thus, although several mechanisms may account for a role of DP4-like peptidases in asthma, detailed information on their anatomical sites of expression and function in lungs is lacking. Therefore, bronchi and lung parenchyma were evaluated using immunohistochemistry and histochemical/enzymatic activity assays, as well as quantitative real-time PCR for this family of peptidases in naïve and asthmatic rat lungs derived from wild-type F344 and DP4-deficient F344 rat strains. Surprisingly, results show not only that the induction of experimental asthma increases DP4 enzymatic activity in the bronchoalveolar lavage fluid and parenchyma, but also that DP8/9 enzymatic activity is regulated and, as well as the expression of DP10, primarily found in the bronchial epithelium of the airways. This is the first report showing a differential and sitespecific DP4-like expression and function in the lungs, suggesting a pathophysiologically significant role in asthma. (J Histochem Cytochem 56:147-155, 2008)

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“…The results established elevated serum DPP-IV activity as a clinically useful marker of cholestasis and demonstrate that DPP-IV levels do not change in metastatic bone disease (Lakatos et al, 1999;Perner et al, 1999) nor in allergic asthmatics, inhaling glucocorticoids or not (Van Der Velden et al, 1999). Higher activities were also found in serum of patients with osteoporosis, probably related to its severity (Gotoh et al, 1988).…”

Section: Discussionmentioning

confidence: 91%

“…Higher activities were also found in serum of patients with osteoporosis, probably related to its severity (Gotoh et al, 1988). However, reduced peptidase can be found in healthy smokers (Van Der Velden et al, 1999), alcoholdependent (Maes et al, 1999) and major depressive (Maes et al, 1997) donors. These last drops are also in agreement with an impaired immune response.…”

Section: Discussionmentioning

confidence: 97%

Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer

et al. 2000

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CD26 is an ectoenzyme with dipeptidyl peptidase IV activity expressed on a variety of cell types. Although the function of the high concentration of serum-soluble CD26 (sCD26) is unknown, it may be related to the cleavage of biologically active polypeptides. As CD26 or enzymatic activity levels were previously associated with cancer, we examined the potential diagnostic and prognostic value of preoperative sCD26 measurements by ELISA in colorectal carcinoma patients. We found a highly significant difference between sCD26 levels in healthy donors (mean 559.7 ± 125.5 μg l –1 ) and cancer patients (mean 261.7 ± 138.1 μg l –1 ) ( P < 0.001). A cut-off at 410 μg l –1 gave 90% sensitivity with 90% specificity which means that the diagnostic efficiency of sCD26 is higher than that shown by other markers, particularly in patients at early stages. Moreover, sCD26 as a variable is not related with Dukes’ stage classification, age, gender, tumour location or degree of differentiation. With a follow-up of 2 years until recurrence, preliminary data show that sCD26 can be managed as a prognostic variable of early carcinoma patients. In addition, the origin of sCD26 is discussed. © 2000 Cancer Research Campaign

show abstract

Peptidase activities in serum and bronchoalveolar lavage fluid from allergic asthmatics — comparison with healthy non‐smokers and smokers and effects of inhaled glucocorticoids

Cited by 31 publications

References 42 publications

Is Dipeptidylpeptidase IV the Missing Link in Angiotensin-Converting Enzyme Inhibitor–Induced Angioedema?

Is Dipeptidylpeptidase IV the Missing Link in Angiotensin-Converting Enzyme Inhibitor–Induced Angioedema?

Regulation of Expression and Function of Dipeptidyl Peptidase 4 (DP4), DP8/9, and DP10 in Allergic Responses of the Lung in Rats

Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer

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