ANNEXIN-I AND ANNEXIN-II BIND TO LIPID-A - A POSSIBLE ROLE IN THE INHIBITION OF ENDOTOXINS

Annexins are Ca2+-dependent phospholipid-binding proteins with anti-in flammatory properties that are present on the surfaces of, and release d from, certain cell types, such as leukocytes and secretory epithelia . The present study investigated the possibility that annexins may bin d directly to bacterial endotoxin, inhibiting its interactions with ce llular receptors or accessory binding proteins. An enzyme-linked immun oassay demonstrated calcium-dependent binding of low nanomolar concent rations of annexin-I and annexin-II p36/p11 heterotetramer to lipid A. In contrast, little or no annexin binding to lipopolysaccharide (LPS) was detected under similar conditions. LPS-binding protein binding to lipid A was blocked by annexin-I, and the annexins inhibited nitrite generation in RAW 264.7 cells induced by lipid A but not that induced by LPS. The data suggest that direct binding of annexins to lipid A ma y represent a mechanism for suppressing cellular and systemic response s to endotoxin.