RESUMEN
Inhibition of the complement system is potentially therapeutic in diseases where uncontrolled or overshooting complement activation plays a significant role in the pathogenesis of the disorder. Calreticulin (CRT) is a multifunctional protein whose cell-surface form (ectocalreticulin) is reported to be a C1q receptor. A 124-residue domain within CRT, the S-domain, binds to C1q, prevents the formation of C1 and so inhibits activation of the classical pathway. To assess the usefulness of CRT S-domain as a complement inhibitor, recombinant S-domain was expressed, radiolabeled, and the fate of the radiolabeled peptide followed in vivo. In rats, CRT-S-domain shows a half-life of 1.21 +/- 0.34 and 40.5 +/- 2.7 min in the distribution and elimination phases from plasma, respectively. The peptide remains largely intact, and is cleared from the circulation by the kidneys, where it accumulates in the proximal convoluted tubules, but is not excreted. Much smaller amounts of the peptide accumulate in other tissues, and essentially none crosses the blood-brain barrier.
