Zymographic Analyses and Measurement of Matrix Metalloproteinase-2 and -9 in Nipple Aspirate Fluids

cular disease (3 ). Such high concentrations of circulating adhesion molecules may be of interest for diagnostic and prognostic purposes, as demonstrated for ICAM-1 and P-selectin, which provide useful information in healthy individuals and in patients with cardiovascular diseases (9 ). However, reference values for healthy children and adults have not been defined. In the current study, we measured serum ICAM-1 and E-, P-, and L-selectin concentrations and determined their age and sex-specific reference intervals over a wide age range (4–55 years) in a healthy population of both sexes. Earlier studies dealing with serum adhesion molecule (ICAM-1 and E-selectin) concentrations in healthy pediatric populations pointed to an age dependency (10–12). In this study, we observed that mean serum ICAM-1 and E-, P-, and L-selectin concentrations steadily decrease during childhood. ICAM-1 and P-selectin concentrations did not vary with age in adulthood, whereas L-selectin decreased in both sexes and E-selectin increased in women only. Although the decrease in adhesion molecule concentrations with age in children has already been described, its physiologic significance during normal development is unknown. Authors of previous studies in adults observed that ICAM-1, E-selectin, and P-selectin concentrations did not vary with age between 18 and 65 years (3, 5, 8, 10, 13, 14), but the decrease in L-selectin during adulthood has not been described. ICAM-1, E-selectin, and P-selectin concentrations display a significant sex dependency only in adults, with men having higher concentrations than women. These sex-related differences, as reported previously in healthy adults (8, 14–16), are probably partly attributable to steroid hormones, especially estrogen. Indeed, healthy postmenopausal women on hormone replacement therapy had lower concentrations of these adhesion molecules than controls not on replacement therapy (7, 17, 18), and in vitro studies have shown negative regulation of adhesion molecule expression by estrogen (19 ). In conclusion, we have shown that serum ICAM-1 and E-, P-, and L-selectin concentrations are age-dependent in childhood and sex-dependent in adulthood. Application of ageand sex-adjusted reference intervals appears to be necessary. These findings emphasize the need to use age(for children) and sex-matched controls (for adults) in all analyses of the possible clinical impact of circulating concentrations of adhesion molecules.