Leukotriene B4 enhances adherence of human polymorphonuclear leukocytes to dermal microvascular endothelial cells in...

Adherence of polymorphonuclear leukocytes (PMNs) to endothelial cells (ECs) is a crucial step in the diapedesis of inflammatory cells to the site of inflammation. We have demonstrated that leukotriene B4 (LTB4), a metabolite of the arachidonic acid cascade, and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) significantly enhance the binding of human PMNs to selected populations of human dermal microvascular endothelial cells (MECs) in vitro. MECs were isolated from the vascular-rich portion of foreskins of newborns. MECs were grown in Iscove's modified Dulbecco's media with 2% prepartum serum and 8% newborn calf serum on 1% gelatin-coated plastic dishes. PMNs isolated from five human donors were added to the culture dishes for varying time intervals (usually 30 min) in the presence and absence of the chemotactic stimuli LTB4 and FMLP. Addition of PMNs to MECs in the absence of chemotactic stimuli results in "baseline" binding to the MEC monolayer. About one in every 150 ECs binds more than five PMNs. These selected ECs are randomly distributed throughout the monolayer. LTB4 from 10(-10) to 10(-7) M increases the number of MECs which selectively bind PMNs by 260% at 10(-7) M. FMLP also increases adherence in qualitatively and quantitatively similar fashion. These data support a role for LTB4 in the mediation of adherence of neutrophils to dermal MECs. In contrast to other endothelial cells from the large blood vessels, such as from umbilical veins or calf thoracic aortae, PMNs bind only to selected MECs in culture, even when stimulated with LTB4 or FMLP.(ABSTRACT TRUNCATED AT 250 WORDS)