Numerous proinflammatory pathways that lead to kidney. HAS2 but not HAS1 expression is enhanced at mononuclear leukocyte invasion have been described in the mRNA level in autoimmune MRL-Faslpr mice, sugrenal disease. These include upregulation of cytokines gesting that HAS2 could mediate the enhanced deposwith ensuing activation of adhesion molecules, stimulaition of HA in the tubulointerstitial compartment in tion of chemokines with subsequent chemotaxis, and autoimmune renal injury [13]. activation of the complement and coagulation cascades The degradation of HA is achieved via cellular uptake that promote leukocyte activation. Recently, we have and lysosomal degradation by specific enzymes in an shown that the enhanced accumulation of the matrix acid cellular compartment. Examining the expression of molecule hyaluronan (HA) in the cortical renal interstitthese Hyal genes, we found that several of these enzymes ium is linked to these classical proinflammatory events are constitutively expressed in the normal kidney. inthekidney. Herewediscusstheconsequencesresulting Transcript levels of Hyal genes are not elevated in from the interaction of HA with its specific cell surface autoimmune lupus mice, suggesting that the Hyal receptor CD44 on renal parenchymal cells. enzymes play a role in the normal turnover of HA by the kidney [15]. The mechanisms of extracellular HA cleavage have not been defined but could involve additional Hyal enzymes or the action of oxygen free radicals