MEASUREMENT OF ENVIRONMENTAL FORMYLMETHIONYL-PEPTIDES

Formylmethionyl-peptides are naturally occurring, biologically active ligands produced by bacteria. They produce a variety of biological eff ects including neutrophil chemotaxis, cellular degranulation, oxygen-f ree radical production, and smooth muscle contraction. Our studies hav e demonstrated that oxidized and reduced forms of formylmethionyl-leuc yl-phenylalanine (fMLP) can be detected in bulk environmental organic dust sampler. Organic dust fMLP content may not reflect total formylme thionyl-peptide content and pathological sequelae. Attempts to develop a total formylmethionyl-peptide assay that would reflect its patholog ical potential have thus far been unsuccessful. information has been d erived concerning the biology of formylmethionyl-peptides from these s tudies. Chromatographic, radioenzymatic, and radioreceptor-ligand bind ing studies were performed. High-performance liquid chromatography (HP LC) analysis of synthetic and environmental fMLP demonstrated that fML P is labile, forming three oxidation products. HPLC is limited by inad equate sensitivity for air sample analysis and the probability of the presence of multiple formylmethionyl-peptides. Deformylases were isola ted from Escherichia coil, but their usefulness in a competitive assay to detect formylmethionyl-peptides was limited by specificity differe nces from that for biological receptors. Receptor binding studies were conducted in an attempt to replace the deformylase with a biological receptor. The receptor binding patterns noted were consistent with the existence of three distinct formylmethionyl-peptide receptor subsets in neutrophils and alveolar macrophages. The plurality of fMLP recepto r subtypes interfered with formylmethionyl-peptide measurement in a co mpetitive assay. Formylmethionyl-peptides may contribute to organic du st-induced disease, but better techniques for the assessment of exposu re to these agents are needed to properly assess their health impact.