Transendothelial cell diapedesis of neutrophils in inflamed human skin

The mode of extravasation of neutrophils (PMNs) in cutaneous inflammation was studied in sequential biopsy specimens taken from human skin. Inflammatory skin reactions were produced by intracutaneous injection of endogeneous mediators of inflammation--C5ades arg, LTB4, neutrophil-activating peptide (NAP) and interleukin-1 (IL-1). Within 30 min after injection neutrophils were observed in close contact with endothelial cells of postcapillary venules and, following cytoplasmic engulfment, the cells were found to be transported transcellulary through the endothelial layer. In a total of 20 biopsy specimens taken at various times, cell migration via interendothelial gaps was absent. Instead, the transcellular pathway appeared to be the first and foremost mode of diapedesis. During this migratory process PMNs lacked signs of degranulation and numerous electron-lucent vesicles and secondary lysosomes were found. In addition, coated pits present on leukocyte as well as endothelial-cell membranes were indicative of receptor-mediated endocytotic processes.