Reliable Evidence of Involvement of the Kinin System in Mouse Malaria

Ohtomo, Hiroshi; Katori, Makoto

doi:10.1254/jjp.22.493

Cited by 15 publications

(7 citation statements)

References 25 publications

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“…In the late 60s, some studies suggested that kinins could be involved in the pathological manifestations of malaria [27-29]. However, these works were not conclusive and, despite the evidences, no more reports correlating kinins with malaria could be found in literature.…”

Section: Discussionmentioning

confidence: 99%

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Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins

Bagnaresi

Barros

Assis

et al. 2012

Malar J

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BackgroundThe malaria burden remains a major public health concern, especially in sub-Saharan Africa. The complex biology of Plasmodium, the apicomplexan parasite responsible for this disease, challenges efforts to develop new strategies to control the disease. Proteolysis is a fundamental process in the metabolism of malaria parasites, but roles for proteases in generating vasoactive peptides have not previously been explored.ResultsIn the present work, it was demonstrated by mass spectrometry analysis that Plasmodium parasites (Plasmodium chabaudi and Plasmodium falciparum) internalize and process plasma kininogen, thereby releasing vasoactive kinins (Lys-BK, BK and des-Arg9-BK) that may mediate haemodynamic alterations during acute malaria. In addition, it was demonstrated that the P. falciparum cysteine proteases falcipain-2 and falcipain-3 generated kinins after incubation with human kininogen, suggesting that these enzymes have an important role in this process. The biologic activity of peptides released by Plasmodium parasites was observed by measuring ileum contraction and activation of kinin receptors (B1 and B2) in HUVEC cells; the peptides elicited an increase in intracellular calcium, measured by Fluo-3 AM fluorescence. This effect was suppressed by the specific receptor antagonists Des-Arg9[Leu8]-BK and HOE-140.ConclusionsIn previously undescribed means of modulating host physiology, it was demonstrated that malaria parasites can generate active kinins by proteolysis of plasma kininogen.

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Section: Discussionmentioning

confidence: 99%

“…Older reports suggested that kinins may be involved in malaria pathology [27,28] and a reduction of plasma kininogen was observed in mice infected by Plasmodium berghei [29]. Nonetheless, the mechanisms by which kinins are generated and the biological effects of released kinins have not previously been reported.…”

Section: Introductionmentioning

confidence: 99%

Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins

Bagnaresi

Barros

Assis

et al. 2012

Malar J

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“…At least 2.39 gg bradykinin equivalents per ml plasma were liberated during the infection (Figure 1). In severe P. knowleei and P. berghei infections (Tella & Maegraith, 1966;Ohtomo & Katori, 1972) marked consumption of kininogen and elevated terminal levels of kinin (Onabanjo & Maegraith, 1971;Ohtomo & Katori, 1972) were found and considered responsible for the peripheral vascular stasis and terminal collapse. Activated kallikrein has been implicated in peripheral vascular changes in both P. knowlesi and B. bovis infections .…”

Section: Discussionmentioning

confidence: 99%

“…At least 2.39 gg bradykinin equivalents per ml plasma were liberated during the infection (Figure 1). In severe P. knowleei and P. berghei infections (Tella & Maegraith, 1966;Ohtomo & Katori, 1972) marked consumption of kininogen and elevated terminal levels of kinin (Onabanjo & Maegraith, 1971;Ohtomo & Katori, 1972) kallikrein has been implicated in peripheral vascular changes in both P. knowlesi and B. bovis infections . Eyre & Lewis (1972) and Eyre, Lewis & Wells (1973) suggested that kinins contribute significantly to the profound hypotension observed during bovine anaphylactic shock.…”

Section: Discussionmentioning

confidence: 99%

KININ, KININOGEN AND KININASE LEVELS DURING ACUTE Babesia bovis (=B. argentina) INFECTION OF CATTLE

Wright

1977

British J Pharmacology

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1Kinin levels began rising on day 3 after infection of cattle with Babesia bovis (=B. argentina) and attained a maximum value of 98% above preinfection levels by day 7. 2 Kininogen levels began falling on day 3 and reached minimum levels of 83% below preinfection levels on day 8. 3 Changes in both kinin and kininogen levels on day 3 coincided with the detection of low levels of parasites, and with a fall in packed cell volume. 4 Plasma kininase levels rose significantly 6 to 9 days after infection. Preparations of lysed and sonicated uninfected and infected red cells contained kininase activity, the respective red cell preparations being 23.9 and 11.4 times more active per mg protein than uninfected red cell preparations. The effect of pH, and the inhibitors disodium edetate, 1,10 phenanthroline and aprotinin on normal and infected plasma and on the various red cell preparations suggested that the rise in plasma kininase levels during infection was probably at least partly due to parasite products. SThese results are discussed in relation to previous data showing that both kallikrein activation and the onset of hypotension also occur on or about day 3.

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“…Ohtomo and Katori (1972) reproduced these data in mice infected by P. berghei . The authors observed that severe cases of malaria infection results in parasitemia elevation, diminished plasmatic kininogen and increased kinin formation, with development of hypotension [ 161 ]. The increase of kinin levels and kininase activity in the acute stages of malarial infection were correlated with circulatory disturbances [ 162 ].…”

Section: Kinins and Their Implication In Protozoan And Parasite Inmentioning

confidence: 99%

Kinins and Their Receptors in Infectious Diseases

2020

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Kinins and their receptors have been implicated in a series of pathological alterations, representing attractive pharmacological targets for several diseases. The present review article aims to discuss the role of the kinin system in infectious diseases. Literature data provides compelling evidence about the participation of kinins in infections caused by diverse agents, including viral, bacterial, fungal, protozoan, and helminth-related ills. It is tempting to propose that modulation of kinin actions and production might be an adjuvant strategy for management of infection-related complications.

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Reliable Evidence of Involvement of the Kinin System in Mouse Malaria

Cited by 15 publications

References 25 publications

Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins

Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins

KININ, KININOGEN AND KININASE LEVELS DURING ACUTE Babesia bovis (=B. argentina) INFECTION OF CATTLE

Kinins and Their Receptors in Infectious Diseases

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