Oversulfated Chondroitin Sulfate, a Contaminant in Heparin Interacts with Contact System, Innate and Adaptive Immunity

Friday, November 08, 2013 — Poster Session IV
2:00 p.m. – 4:00 p.m.	FAES Academic Center (Upper-Level Terrace)	FDA/CBER	IMMUNO-32

Authors

Z-H Zhou
E Karnaukhova
M Rajabi
K Reeder
T Chen
S Dhawan
S Kozlowski

Abstract

Oversulfated chondroitin sulfate (OSCS), a contaminant in heparin that induced the 2008 heparin adverse events in the US, has become the subject of multidisciplinary investigation. In our previous studies, we found OSCS inhibited complement fixation on bacteria and bacterial lysis mediated by the complement classical pathway by potentiating C1 inhibitor while the level of C1 inhibitor in the plasma has a great impact on the OSCS-induced kallikrein activity of the contact system and both may link to infection and adverse events. In this study, by using surface plasmon resonance (Biacore) assay, we found OSCS interacts with adaptive immunity through binding with a panel of T cell chemokines. Flow cytometry demonstrated that OSCS binding blocks chemokine-induced calcium mobilization and T cell migration. ImageStream technique further revealed that T cell polarization mediated by chemokines is also modulated. We concluded that the OSCS, a contaminant in heparin, had a broad interaction with human contact system and immune system, which may reveal new mechanisms of heparin-induced clinical adverse events.