Histamine-induced changes in the actin cytoskeleton of the human microvascular endothelial cell line HMEC-1

Increased permeability of the microvascular endothelium is a component of t he inflammatory response. inflammatory mediators such as histamine contribu te to this permeability change. Modulation of cytoskeletal F-actin has been implicated as part of the cellular mechanism involved. Permeability change s occur predominantly at the microvascular level while the majority of curr ent knowledge stems from research on cells from large vessels. We have ther efore utilized an immortalized human dermal microvascular cell line, HMEC-1 . Confluent monolayers were exposed to histamine (10 mu M. 100 mu M) for 1, 5, 10 or 15 minutes. F-Actin changes were detected by labelling with FITC- conjugated phalloidin. Histamine exposure resulted in the rounding of cells with the formation of intercellular gaps. The percentage of rounded cells and the number of gaps increased with exposure time. F-actin was redistribu ted from a peripheral band in control cultures to a perinuclear zone. Conti nual presence of the agonist was required for these phenotypic changes to o ccur. Removal of histamine caused reversal of these observations. Cells exp osed to histamine for 1 minute needed 15 minutes to recover their normal mo rphology and F-actin distribution. These reversible effects suggest that F- actin redistribution maybe part of the microvascular cell response to hista mine. (C) 1999 Elsevier Science Ltd. All rights reserved.