Abhilasha, K. V. and Sumanth, M. S. and Anita, T. and Ravi Prakash, S. and Kemparaju, K. and Marathe, Gopal K. (2020) Reversible cross-tolerance to platelet-activating factor signaling by bacterial toxins. Platelets, 32 (7). ISSN 1369-1635
Full text not available from this repository. (Request a copy)Abstract
Bacterial toxins signaling through Toll-like receptors (TLRs) are implicated in the pathogenesis of many inflammatory diseases. Among the toxins, lipopolysaccharide (LPS) exerts its action via TLR-4 while lipoteichoic acid (LTA) and bacterial lipoproteins such as Braun lipoprotein (BLP) or its synthetic analogue Pam3CSK4 act through TLR-2. Part of the TLR mediated pathogenicity is believed to stem from endogenously biosynthesized platelet-activating factor (PAF)- a potent inflammatory phospholipid acting through PAF-receptor (PAF-R). However, the role of PAF in inflammatory diseases like endotoxemia is controversial. In order to test the direct contribution of PAF in TLR-mediated pathogenicity, we intraperitoneally injected PAF to Wistar albino mice in the presence or absence of bacterial toxins. Intraperitoneal injection of PAF (5 mu g/mouse) causes sudden death of mice, that can be delayed by simultaneously or pre-treating the animals with high doses of bacterial toxins- a phenomenon known as endotoxin cross-tolerance. The bacterial toxins- induced tolerance to PAF can be reversed by increasing the concentration of PAF suggesting the reversibility of cross-tolerance. We did similar experiments using human platelets that express both canonical PAF-R and TLRs. Although bacterial toxins did not induce human platelet aggregation, they inhibited PAF-induced platelet aggregation in a reversible manner. Using rabbit platelets that are ultrasensitive to PAF, we found bacterial toxins (LPS and LTA) and Pam3CSK4 causing rabbit platelet aggregation via PAF-R dependent way. The physical interaction of PAF-R and bacterial toxins is also demonstrated in a human epidermal cell line having stable PAF-R expression. Thus, we suggest the possibility of direct physical interaction of bacterial toxins with PAF-R leading to cross-tolerance.
| Item Type: | Article |
|---|---|
| Subjects: | C Chemical Science > Biochemistry |
| Divisions: | Department of > Biochemistry |
| Depositing User: | Mr Umendra uom |
| Date Deposited: | 05 Mar 2021 05:31 |
| Last Modified: | 23 Jun 2022 06:54 |
| URI: | http://eprints.uni-mysore.ac.in/id/eprint/15528 |
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