Trypanostatic Activity of Rat IgG Purified from the Surface Coat of Trypanosoma lewisi

Giannini, Suzanne Holmes; D'Alesandro, Philip A.

doi:10.2307/3280981

Cited by 16 publications

(13 citation statements)

References 17 publications

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“…In particular, adult forms isolated from immunocompetent animals bear considerably more membrane immunoglobulin G than dividing forms from immunosuppressed animals (6,7). At least some of this membrane immunoglobulin G is ablastin, a specific antitrypanosome antibody (8). Whether the surface proteins which restrict the effects of the ACP on intact trypanosomes also restrict antibody-dependent, complement-mediated lysis or macrophage ingestion of immunoglobulin G-coated trypanosomes deserves further attention.…”

Section: Vol 42 1983mentioning

confidence: 99%

Externally disposed membrane polypeptides of intact and protease-treated Trypanosoma lewisi correlated with sensitivity to alternate complement pathway-mediated lysis

Sturtevant¹,

Balber²

1983

Infect Immun

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Reproducing forms of Trypanosoma lewisi isolated from X-irradiated rats and adult forms from intact rats were not lysed by fresh mammalian sera. Treating parasites with trypsin or chymotrypsin, but not with neuraminidase, under conditions which did not impair viability rendered the parasites sensitive to lysis by rat, mouse, rabbit, and human sera. Serum from animal strains or humans genetically deficient in complement component C3, C5, or C6 did not lyse protease-treated parasites. The lytic factors in serum displayed the heat sensitivity and the Mg2+ requirement characteristic of the alternate complement pathway. Lysis was resolved into two phases, Mg2'-dependent binding of serum factors to parasites and subsequent C5-dependent, Mg2+-independent lysis. Allowing protease-treated parasites to readsorb host proteins did not block lysis by serum. Protease-treated parasites regenerated components which prevented complement-mediated lysis during 2 h in culture at 37°C. This regeneration was inhibited by cycloheximide but not by tunicamycin. Ten major components were resolved in radioautographs of sodium dodecyl sulfate-polyacrylamide gels of extracts of radioiodinated intact cells. Protease treatment before radioiodination reduced the amount of radioactivity associated with these components disproportionately. Components with apparent molecular weights of 102,000, 88,000, and 47,000 were strongly labeled in intact cells, poorly labeled after enzyme treatment, and again labeled in cells that were cultured at 37°C after enzyme treatment. Cycloheximide blocked the reappearance of these components on cultured cells. The presence of these three components was therefore correlated with resistance to complementmediated lysis.

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Section: Vol 42 1983mentioning

confidence: 99%

Externally disposed membrane polypeptides of intact and protease-treated Trypanosoma lewisi correlated with sensitivity to alternate complement pathway-mediated lysis

Sturtevant¹,

Balber²

1983

Infect Immun

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“…More recently. Giannini and D'Alesandro (1982) have reported that IgG prepared from the surface coat of T. lewisi harvested from normal rats contains ablastinic activity. However, the question remains as to why adult trypanosomes.…”

Section: Discussionmentioning

confidence: 99%

“…The nature and mode of action of ablastin is not clear, although there has been considerable discussion on whether or not it is an IgG molecule Clarkson, 19K0: Hsu andDusanic. 1982rDrew andJenkin, 1982;Giannini and D'Alesandro. 1982).…”

Section: Introductionmentioning

confidence: 99%

TRYPANOSOMA LEWISI: THE EFFECT OF THYMECTOMY ON THE PRODUCTION OF ABLASTIN AND THE TERMINATION OF THE PARASITAEMIA IN INFECTED RATS

Drew

Jenkin

1984

Aust J Exp Biol Med

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Suminar>'. This study invesligalcti the efTect of the depletion of T lymphocytes on liie production of iiblastin ;ind the termination of the parasitaeniios in Ponon strain rats infected with Trypanosoma Icwisi. Weanling rats were thymectomised or sham-thymcciomiscd and then X-irradiated. AHer allowing 96 days for recovery from these procedures the rats were infected with T. lewisi. The rats were considered to be T lymphocyte depleted if ihcy were unable to mount an antibody response to sheep red blood cells before the infection, a delayed type hypersensitivity response to trypanosomal antigen after they had cleared tlic infeciion. and if they succtimbed to subsequent challenge with an intracelliilar bacterial parasite. Salmonella typhimuniim C5. The T lymphocyte depleted rats were foimd to have no macroscopic thymiis rcmnanis visible at autopsy. The shamthymcctomiscd and iinoperated control rats retained all the T lymphocyte funclions tested for. There was no difference between ihe control and the T lymphocyte depleted rals in ihe ability to eliminate the parasite following infection wiih T. /cH'/.v/. Abla^tin tilrcs in the serum, mcasurcit by a sensitive in viiro assay. uere found to be the same in each of the groups of rais tested, regardless of iheir T lymphocyie status. It is concluded that T lymphocytes are not essential for rals lo eliminate a T. IcH-isi infection, nor for the production of ablastin. INTRODUCTIONTrypanosoma lewis! infection in healthy rats results in a self-litniting, sytiiptomlcss disease. The parasite is fnund unly in the bloodstream of the rat, where it multiplies rapidly for about a week before an antibody-mediated first crisis considerably reduces the parasitaemia. This is followed by a low level parasitaemia in whieh the parasite eireulates as an adult form, nondividing and uniform in size and shape. Depending on the strain of rat and parasite, this adult phase may last for a period of from several days to over a year (unpublished observations). During an antibody-mediated seeond crisis the adult parasite is elitninated from the rat. It is rep;>rted that each crisis is accompanied by a specific antibody response. The first antibody is speeifie for division forms and cannot be adsorbed from serum by the adult parasite, while the second contains antibodies directed against the non-reproducing fortTts present late in the infection (Coventry, 1930). Both antibodies

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“…This IgG plays two unusual roles. First, surface IgG (sIgG) has ablastic activity (7,20). Ablastin, an IgG antibody activity that appears early in week 1 of infection, transforms the reproducing parasites present in the blood at this time into morphologically (5,31), antigenically (6), and physiologically (10,26,29) distinct, nonreproducing adult forms.…”

mentioning

confidence: 99%

A surface glycoprotein of Trypanosoma lewisi binds immunoglobulin G from the serum of uninfected rats

Balber¹,

Sturtevant²

1986

Infect Immun

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Detergent extracts of whole Trypanosoma lewisi were fractionated by polyacrylamide gel electrophoresis and transferred to nitrocellulose for immunoblotting analysis. Antibody probes to rat immunoglobulin G (IgG) and IgM detected intact y chains, , chains, and light chains in extracts. The amount of immunoglobulin detected increased as the infection progressed. Transfers were also incubated in serum from conventionally reared (CRS), specific-pathogen-free (SPFS), or germ-free rats before being probed with anti-rat IgG or anti-rat IgM. Components of 200, 175, and 120 kilodaltons (kDa) bound IgM from all sera tested and were present in extracts of trypanosomes isolated from lethally irradiated or intact rats on different days during infection. No parasite components bound IgG from serum of germ-free rats. However, 145-, 175-, and 200-kDa components bound IgG from CRS and SPFS. A 74-kDa protein was the major IgG-binding component in extracts of reproducing parasites. This component bound much more IgG from CRS than it bound from SPFS. The 74-kDa protein was removed from parasites by mild trypsinization and corresponded to a major surface glycoprotein detected when intact cells were radioiodinated. These results indicate that natural antibodies to T. lewisi exist in rats or that these parasites have surface proteins that bind immunoglobulins without regard to antigenic specificity.

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Trypanostatic Activity of Rat IgG Purified from the Surface Coat of Trypanosoma lewisi

Cited by 16 publications

References 17 publications

Externally disposed membrane polypeptides of intact and protease-treated Trypanosoma lewisi correlated with sensitivity to alternate complement pathway-mediated lysis

Externally disposed membrane polypeptides of intact and protease-treated Trypanosoma lewisi correlated with sensitivity to alternate complement pathway-mediated lysis

TRYPANOSOMA LEWISI: THE EFFECT OF THYMECTOMY ON THE PRODUCTION OF ABLASTIN AND THE TERMINATION OF THE PARASITAEMIA IN INFECTED RATS

A surface glycoprotein of Trypanosoma lewisi binds immunoglobulin G from the serum of uninfected rats

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