Induction of nephrocalcinosis in rabbit kidneys after long-term exposure to a streptococcal teichoic acid

This study was performed to determine whether antibody-dependent cellular cytotoxicity (ADCC) could be directed against mammalian cells sensitized with spontaneously adhering bacterial substances. 51Cr-labeled SB leukemia cells were incubated with purified S43 group A streptococcal lipoteichoic acid (LTA; 0.001 to 100 ,ug/ml). Purified leukocyte ADCC effector cells were added to the LTA-coated target cells at various effector-to-target ratois (100:1 to 12:1), followed by the addition of rabbit anti-LTA. After incubation for 4 h, target cell lysis was calculated based on the release of label into the medium. As little as 1 ng of LTA per ml was sufficient to sensitize the target cells to ADCC lysis (12%); however, concentrations above 0.1 ,ug/ml generally resulted in 60 to 80% lysis. LTA alone was not cytotoxic to these target cells. Targeting did not occur if effector cells were sensitized or if free LTA was added to the medium. Specificity was demonstrated by cold-target inhibition, which showed that anti-LTA cytotoxicity could be inhibited only by unlabeled, LTA-treated target cells but not by cold SB cells alone. The findings indicate that certain soluble bacterial components, when bound to mammalian cells in the presence of specific antibody, can target ADCC effectors to these cells. This mechanism may be an important factor in the delayed sequelae of bacterial infections. * Corresponding author. t Present address: Pharmaceutical Research and Development, Bristol-Myers Co., Syracuse, NY 13221-4755.

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confidence: 99%

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confidence: 99%

Pretreatment with lipoteichoic acid sensitizes target cells to antibody-dependent cellular cytotoxicity in the presence of anti-lipoteichoic acid antibodies

Lopatin¹,

Kessler²

1985

“…The binding of LTA to host cell membranes is of special interest because of the potential role of LTA in the initiation of inflammatory diseases. Injections of LTA have been shown to produce arthritis (13) and nephritis (19) in laboratory animals, presumably by binding to the respective organ tissues and producing local immunotoxic reactions (8). It has been suggested by Wicken and Knox (8,20) that LTA may serve to carry various streptococcal antigens and to bind them to vital organ tissues.…”

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confidence: 99%

Binding of lipoteichoic acid of group A streptococci to isolated human erythrocyte membranes

Chiang¹,

Alkan²,

Beachey³

1979

The spontaneous binding of group A streptococcal lipoteichoic acid (LTA) to mammalian cell membranes was studied in isolated membranes of human erythrocytes. The binding of radiolabeled LTA to erythrocyte membranes was dependent on membrane concentration and time. Binding approached a maximum within 30 min of incubation. The bound LTA could be displaced by adding a 50-fold excess of unlabeled LTA. The displaced LTA was eluted from a column of Sepharose 6B in a position identical to that of authentic LTA, suggesting that binding did not alter the size of the molecule. A dissociation constant of 42 [iM was calculated, and only one population of approximately 5.5 x 106 binding sites per erythrocyte membrane was detected. Since these results suggested that erythrocyte membranes possess specific binding sites for LTA, an attempt was made to localize the putative receptors to the outside or the inside surface of the erythrocyte membrane. Assays of the binding of LTA to resealed right-side-out and inside-out membrane ghosts demonstrated that the outside surface was able to bind over 10 times more LTA than the inside surface. These results support the concept that the membranes possess specific binding sites for LTA and indicate that these binding sites are located almost entirely on the outside surface of erythrocyte membranes.

“…The lipid-associated glycerol teichoic acid (LTA) from the group A streptococcus 1-RP41 has been shown to inhibit the anti-sheep erythrocyte antibody response and enhance the Escherichia coli anti-lipopolysaccharide response in mice (3) and to stimulate the phagocytic activity of mouse peritoneal cells (4). Moreover, LTA has been implicated in an allergic haptenic hypersensitivity (1), the induction of immune complex nephropathy (Fiedel and Jackson, submitted for publication), and the formation of renal calculi in rabbits (6). In the course of studies to assess the capacity of counterion complexes to activate the complement system in a manner analogous to antigen-antibody complexes (2), it was observed that counterion complexes between LTA and the polycation protamine (PC) resulted in the consumption of whole complement (CH50) activity in human serum (Fig.…”

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confidence: 99%

“…In view of a recent report that teichoic acid obtained from an unencapsulated pneumococcus, strain R36A, may activate the alternative complement pathway in guinea pig sera (7), attempts were made to assess such a possibility for LTA in the human system by using the rabbit erythrocyte alternative pathway hemolytic assay as described by Platts-Mills and Ishizaka (5); the results are presented in acterization of LTA were performed as described previously (1,3,4,6). Buffers, preincubation conditions, and CH5o assays were prepared and performed also as described previously (2); PC was obtained commercially.…”

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confidence: 99%

Activation of the alternative complement pathway by a streptococcal lipoteichoic acid

Fiedel¹,

Jackson²

1978

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