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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peritrophic matrix (PM) that forms around a blood meal is a potential barrier of Plasmodium development in mosquitoes. Previously, we have shown that to traverse the PM, Plasmodium ookinetes secrete a prochitinase and that an inhibitor of chitinase blocks further parasite development. Here we report that it is the mosquito trypsin that activates the Plasmodium prochitinase. Trypsin was identified as the chitinase-activating enzyme by two criteria: (i) trypsin activity and activating activity comigrated on one-dimensional gels, and (ii) activating activity and penetration of the PM by Plasmodium parasites were both hindered by trypsin-specific inhibitors. Subsequently, we examined the effect of antitrypsin antibodies on the parasite life cycle. Antibodies prepared against a recombinant blackfly trypsin effectively and specifically inhibited mosquito trypsin activity. Moreover, when incorporated into an infective blood meal, the antitrypsin antibodies blocked infectivity of Aedes aegypti mosquitoes by Plasmodium gallinaceum. This block of infectivity could be reversed by exogenously provided chitinase, strongly suggesting that the antibodies act by inhibiting prochitinase activation and not on the parasite itself. This work led to the identification of a mosquito antigen, i.e., midgut trypsin, as a novel target for blocking malaria transmission.
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PMID:Antibody-mediated inhibition of Aedes aegypti midgut trypsins blocks sporogonic development of Plasmodium gallinaceum. 864 75

Trypsin production in the malaria vector Anopheles tessellatus Theobald peaks between 12 and 21 h after a blood meal. The presence of leupeptin or soybean trypsin inhibitor in a blood meal delayed the onset of maximal trypsin activity. Trypsin inhibitors in an infective blood meal increased the infectivity of Plasmodium vivax Grassi and decreased infectivity of P. falciparum Welch to An tessellatus. The opposite effects of trypsin inhibitors on infectivity of the 2 malaria parasites were attributed to differences in the biology of the parasites within the midgut of the vector, particularly the time of ookinete formation and the requirement for activation of a chitinase.
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PMID:Different effects of modulation of mosquito (Diptera:Culicidae) trypsin activity on the infectivity of two human malaria (Hemosporidia:Plasmodidae) parasites. 884 Jun 84

In areas of high Plasmodium falciparum transmission, immunity to malaria is acquired during childhood, so that adults in general are clinically immune. One exception is that first-time pregnant women are susceptible to pregnancy-associated malaria caused by accumulation of parasites in the placenta. Pregnancy-associated variant surface antigens (VSAPAM) mediate binding of the infected erythrocyte to chondroitin sulphate proteoglycans in the placental intervillous space. Several lines of evidence indicate that the molecular identity of VSAPAM is VAR2CSA, a relatively conserved member of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. While native PfEMP1 molecules expressed on the infected erythrocyte surface generally are sensitive to mild trypsinization, some VSAPAM expressing parasite lines are resistant. This finding has led to the suggestion that molecules other than PfEMP1, or at least several different PfEMP1 families mediate the VSAPAM phenotype. To address this issue we incubated three different VAR2CSA expressing parasite lines with trypsin and found that polymorphic VAR2CSA variants can be both protease resistant and sensitive. Trypsin treatment resulted in loss of ability to adhere to CSA and loss of sex-specific antibody recognition of the surface of the infected erythrocyte in one sensitive isolate, whereas CSA binding and sex-specific recognition were largely unaffected by trypsin treatment in two resistant isolates. These results support the hypothesis that VAR2CSA mediates the adhesive and antigenic phenotypes shown by parasites causing placental malaria.
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PMID:Plasmodium falciparum: VAR2CSA expressed during pregnancy-associated malaria is partially resistant to proteolytic cleavage by trypsin. 1744 5

This study examined the ability of P.falciparum-infected erythrocytes (IE) to induce a pro-adhesive environment in the host endothelium during malaria infection, prior to the systemic cytokine activation seen in the later phase of disease. Previous work had shown increases in receptor levels but had not measured to actual impact on IE binding. Using a co-culture system with a range of endothelial cells (EC) and IE with different cytoadherent properties, we have characterised the specific expression of adhesion receptors and subsequent IE binding by FACS and adhesion assays. We have also examined the specific signalling pathways induced during co-culture that are potentially involved in the induction of receptor expression. The results confirmed that ICAM-1 is up-regulated, albeit at much lower levels than seen with TNF activation, in response to co-culture with infected erythrocytes in all three tissue endothelial cell types tested but that up-regulation of VCAM-1 is tissue-dependent. This small increase in the levels of EC receptors correlated with large changes in IE adhesion ability. Co-culture with either RBC or IE increased the potential of subsequent adhesion indicating priming/modulation effects on EC which make them more susceptible to adhesion and thereby the recruitment of IE. Trypsin surface digestion of IE and the use of a Pfsbp1-knockout (ko) parasite line abrogated the up-regulation of ICAM-1 and reduced IE binding to EC suggesting that PfEMP-1 and other molecules exported to the IE surface via the PfSBP1 pathway are major mediators of this phenotype. This was also supported by the higher induction of EC adhesion receptors by adherent IE compared to isogenic, non-adherent lines.
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PMID:Amplification of P. falciparum Cytoadherence through induction of a pro-adhesive state in host endothelium. 2204 76