CHARACTERIZATION OF E-SELECTIN EXPRESSION, LEUKOCYTE TRAFFIC AND CLINICAL SEQUELAE IN URATE CRYSTAL-INDUCED INFLAMMATION - AN INSIGHT INTO GOUT

The self-limiting response to urate crystals allows the exploration of events involved in both the onset and resolution of gout. Using i.v. injected radiolabelled anti-E-selectin monoclonal antibody 1.2B6 toget her with differentially radiolabelled neutrophils, mononuclear cells a nd albumin, we have characterized the expression of E-selectin in rela tion to leucocyte traffic, microvascular permeability and clinical seq uelae following intracutaneous injection of monosodium urate crystals. We found that the inflammatory response in this model involved severa l distinct phases. First, E-selectin expression increased over 2-6 h i n the context of increases in neutrophil and mononuclear cell accumula tion, and albumin leakage. Secondly, leucocyte accumulation rapidly de clined despite persisting E-selectin expression. Thirdly, E-selectin e xpression peaked at similar to 8 h and then fell despite an increase i n clinically detectable erythema and induration. Lastly, these clinica l manifestations of inflammation resolved despite the continued presen ce of urate crystals in the tissues. The further dissection of mechani sms regulating these phases will lead to a better understanding of eve nts in both the pathogenesis and resolution of gout. Of broader signif icance, this inflammatory model may yield information about the protec tive events that underly resolution of inflammation and provide insigh ts into factors which determine chronicity.