Junctional apparatus in erythrocytes infected with malarial parasites

Aikawa, Masamichi; Rabbege, John; Wellde, B. T.

doi:10.1007/bf00981942

Cited by 25 publications

(6 citation statements)

References 6 publications

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“…In contrast (Fig. 5B), when knobs were present, junctions (6) were found (arrows), accompanied many times by a discontinuous membrane structure of the endothelial cell. These characteristics were observed even when early trophozoites with less developed knobs (Fig.…”

Section: Direct Observation Of Microcirculatory Flow and Electronmentioning

confidence: 90%

“…The mechanism of the P. falciparum-induced microvascular obstruction is not clearly understood; both the capability of malaria parasite-infected erythrocytes to produce aggregates through cell-cell interactions (4) as well as parasitized erythrocyte-endothelial cell interaction (5,6) have been suggested as mechanisms for the vascular entrapment of parasitized cells. Knobs found in the membranes of malariainfected erythrocytes (7) have been proposed as the specific structures involved in both possible mechanisms.…”

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confidence: 99%

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Membrane knobs are required for the microcirculatory obstruction induced by Plasmodium falciparum-infected erythrocytes.

Raventós-Suárez

Kaul

Macaluso³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

121

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We have studied the pathophysiology of the vascular obstruction induced by Plasmodumfalkiparum-parasitized erythrocytes with the use of an ex vivo microcirculatory preparation perfused with red cells infected with knobless and knobby dones of the FCR-3 strain. We find that parasitized erythrocyte membrane knobs are indispensable for the generation of the circulatory obstruction. Uninfected erythrocytes incubated in culture and erythrocytes infected with early or late forms of the knobless dones or the early forms of the knobby done all failed to obstruct the microcirculation, although exhibiting various effects on bulk viscosity and peripheral resistance during flow. In contrast, late forms of the knobby clone produced significantly higher peripheral resistance during flow and significant obstruction as detected by changes in time of pressure flow recovery as well as by direct videorecorded microscopic observation. Optical and electron microscopy showed that the adherence of parasitized cells to the endothelium was limited to the venules and involved the knobs in junctions. In addition, we were able to follow the sequence of events during obstruction: initial red-cell adherence to the venular endothelium (sometimes only transitory) followed by progressive recruitment at the venule surface, finally leading to total obstruction that involved parasitized and nonparasitized erythrocytes. Sometimes, retrograde aggregation would extend the obstruction to the capillaries or even precapillary arterioles. These results show that knobs are necessary and sufficient to produce vascular obstruction and that other factors (spleen, immunological, etc.) can only have a modulating role. These results also exclude the possibility that the exclusive adherence to venules is the consequence of "plasma factors"found in the malaric patients.The infection caused by Plasmodium falciparum produces the most severe form of human malaria (1) The mechanism of the P. falciparum-induced microvascular obstruction is not clearly understood; both the capability of malaria parasite-infected erythrocytes to produce aggregates through cell-cell interactions (4) as well as parasitized erythrocyte-endothelial cell interaction (5, 6) have been suggested as mechanisms for the vascular entrapment of parasitized cells. Knobs found in the membranes of malariainfected erythrocytes (7) have been proposed as the specific structures involved in both possible mechanisms. Decreased red cell deformability secondary to increased viscosity of parasitized red cells may also play a role in obstruction (8).The work presented here attempts to dissect the differential contribution of erythrocyte membrane knobs, decreased deformability, and aggregation (clumping of parasitized and nonparasitized cells) to the pathophysiology of the microcirculation obstruction induced by P. falciparum malaria infection. Our experimental design makes use of an isolated vasculature preparation of the rat mesoappendix [Baez preparation (9)] artificially perfused with P. falciparum-...

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Section: Direct Observation Of Microcirculatory Flow and Electronmentioning

confidence: 90%

mentioning

confidence: 99%

Membrane knobs are required for the microcirculatory obstruction induced by Plasmodium falciparum-infected erythrocytes.

Raventós-Suárez

Kaul

Macaluso³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

121

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“…The KAHRP gene product is a component of the knob structure on the surface of parasitized erythrocytes that are responsible for cytoadherence (12,13). Chromosomal breakage events disrupting the KAHRP gene result in parasite mutants that are knobless and cytoadherentdeficient (14,15,16).…”

Section: Introductionmentioning

confidence: 99%

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum

et al. 1994

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“…In vivo and in vitro, the adherence of IE mediated by junction formation between an area localized over electron dense protrusions (knobs) ( 13) in the infected erythrocyte membrane and the endothelial cell membrane (8,14). It has been previously shown that an MAb, OKM5 (10), inhibits the in vitro cytoadherence of P. falciparum IE to these specific human target cells.…”

Section: Introductionmentioning

confidence: 99%

A human 88-kD membrane glycoprotein (CD36) functions in vitro as a receptor for a cytoadherence ligand on Plasmodium falciparum-infected erythrocytes.

et al. 1989

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Plasmodium falciparum-infected erythrocytes (IE) specifically adhere to vascular endothelium in vivo and to human endothelial cells, some human melanoma cell lines, and human monocytes in vitro. The tissue cell receptor for a ligand on the surface of the infected erythrocytes is an Mr 88,000 glycoprotein (GP88) recognized by the MAb OKM5, which also blocks cytoadherence of IE. Isolated, affinity-purified GP88 (CD36) competitively blocks cytoadherence and when absorbed to plastic surfaces, specifically binds P. falciparum IE. Additionally, monoclonal and polyclonal antibodies to GP88 block cytoadherence to both target cells and immobilized GP88. Binding to GP88 by IE is unaffected by the absence of calcium or the absence of thrombospondin, a putative mediator for cytoadherence of P. falciparum IE. Thus, GP88 (CD36), which has been demonstrated to be the same as platelet glycoprotein IV, interacts directly with P. falciparum IE, presumably via a parasite-induced ligand exposed on the surface of the infected erythrocytes. CD36 is shown to be present on brain endothelium in both individuals without malaria and individuals with cerebral malaria. This would suggest that factors other than just cerebral sequestration of IE play an initiating role in the genesis of cerebral malaria.

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Junctional apparatus in erythrocytes infected with malarial parasites

Cited by 25 publications

References 6 publications

Membrane knobs are required for the microcirculatory obstruction induced by Plasmodium falciparum-infected erythrocytes.

Membrane knobs are required for the microcirculatory obstruction induced by Plasmodium falciparum-infected erythrocytes.

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum

A human 88-kD membrane glycoprotein (CD36) functions in vitro as a receptor for a cytoadherence ligand on Plasmodium falciparum-infected erythrocytes.

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