title: Retinol inhibition of in vitro human neutrophil superoxide anion release.
abstract: Retinol deficiency has been clinically associated with visual impairment as well as altered growth and differentiation of various epithelial cell populations. An additional factor that may be operative in the setting of retinol deficiency is impaired immunomodulation of the neutrophil inflammatory response. Our study demonstrated a concentration-dependent inhibition by retinol of activated neutrophil superoxide anion (O2.-) release. Concentration of drug (retinol) causing 50% inhibition of initial velocity O2.- production (IC50) was 42.6 +/- 10.9 microM. Latter phases of the O2.- release reaction displayed significantly lower IC50 values. Similarly, as time of retinol-neutrophil incubation was increased, IC50 decreased. Retinol inhibition of neutrophil O2.- did not appear to involve activation/desensitization, cytotoxicity, or free-radical scavenging mechanisms. Retinol was shown to inhibit intact PMN O2.- release even after addition of the respiratory burst stimulus. Moreover, retinol inhibited O2.- release in membranes isolated from activated neutrophils. In addition to promoting proper organization and differentiation of epithelial cells, appropriate plasma/tissue retinol levels may also modulate the neutrophil tissue inflammatory response.
authors.affiliation: University of Wisconsin Children's Hospital, Division of Critical Care Medicine, Madison 53792.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.forename: J R
authors.initials: JR
authors.lastname: Lewandoski
authors.forename: J J
authors.initials: JJ
authors.lastname: Zimmerman
mesh_terms: D000328:Adult; D001997:Bronchopulmonary Dysplasia / Q000209:etiology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007249:Inflammation / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D014801:Vitamin A / Q000494:pharmacology*; D014802:Vitamin A Deficiency / Q000150:complications / Q000276:immunology
chemical_list: D013481:Superoxides; D014801:Vitamin A