Design and Implementation of a Common Currency Area in the East African Community

Abstract

We tested the hypothesis that the artificial addition of heavy chains (HCs) from inter-α-inhibitor (IαI) to hyaluronan (HA), by adding recombinant tumor-necrosis-factor-induced-protein-6 (TSG-6) to the culturing media of murine airway smooth muscle (MASM) cells, would enhance leukocyte binding to HA cables produced in response to polyinosinic-polycytidylic acid (Poly(I:C)). As predicted, the addition of HCs to HA cables enhanced leukocyte adhesion to these cables, but it also had several unexpected effects: (i) It produced thicker, more pronounced, HA cables. (ii) It increased the accumulation of HA in the cell-associated matrix. and, (iii) It decreased the amount of HA in the conditioned media. Importantly, these effects were only observed when TSG-6 was administered in the presence of Poly(I:C) and did not exert any effect on its own. These phenomena occurred during active, Poly(I:C) - induced, HA synthesis, and did not occur when TSG-6 was added after Poly(I:C) - induced HA synthesis had completed. MASM cells derived from TSG-6 null, HAS1/3 null and CD44 null mice amplified HA synthesis in response to Poly(I:C) + TSG-6 in a manner similar to WT MASM, demonstrating that they are expendable in this process. We conclude that TSG-6 increases the accumulation of HA in the cell-associated matrix, partially by preventing its dissolution from the cell-associated matrix into the conditioned media, but primarily by also inducing HA synthesis.