Stimulation of lymphocyte migration by a novel low-molecular weight compound in normal human skin and plasma

Normal human skin contains an extravascular population of lymphocytes which have been proposed to play a central role in immunosurveillance. The hypothesis that physiologic lymphocyte chemoattractants induce the migration of these cells has been tested by analysis of samples from normal human skin by an in vitro lymphocyte migration assay in combination with high-performance liquid chromatography (HPLC). Dilution-related lymphocyte migration was seen on assay of aqueous extracts of stratum corneum, analysis after ultrafiltration consistently demonstrating activity in less than 1-kDa fractions. Similar results were obtained with chamber fluid from abraded normal skin and with normal plasma. A novel, polar, low-molecular weight component in plasma and chamber fluid was purified to homogeneity by reverse-phase HPLC. Material from the two sources possessed identical retention times on reverse-phase HPLC and similar ultraviolet (UV) absorbance spectra (UV maximum 274 nm). The factor has been termed plasma-associated lymphocyte chemoattractant (PALC). When purified to homogeneity, PALC induced concentration-related lymphocyte migration, was extractable in lipid solvents and was not peptide in nature, as determined by mass spectrometric and amino acid analyses and proteolytic enzyme digestion. It is proposed that PALC may play a role in mediating physiologic margination, adherence and migration of lymphocytes in normal human skin.