Vol. 287, Issue 2, 640-647, November 1998

Characterization of the Polymorphonuclear Leukocyte-Induced Vasoconstriction in Isolated Human Umbilical Veins

Steven W. Kerr, Rebecca Yu¹, Carol D. Stearns, Nancy A. Haynes and Raymond J. Winquist

Department of Immunological Diseases, Research and Development Center, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut

We investigated the contractile effects of both activated and unactivated polymorphonuclear leukocytes (PMNs) on human vascular tissue to characterize the influence of human PMNs on vascular tone. PMNs were added either unactivated or after f-met-leu-phe (fMLP) activation (10⁸ M), into tissue chambers containing human umbilical vein segments under either control or cytokine-treated conditions. The activation state of different PMN preparations was measured by immunofluorescence staining of the adhesion glycoproteins Mac-1 and L-selectin. Both unactivated and activated PMNs induced a cell number-dependent (1.5 × 10⁵ to 2 × 10⁶ cells/ml) vasoconstriction in human umbilical vein segments. This PMN-induced response was not inhibited by treatment with indomethacin (10⁵ M), superoxide dismutase (2 × 10⁷ M) or L-nitro-monomethyl arginine (10⁴ M). However, treatment of PMNs with the leukotriene biosynthesis inhibitor BIRM-270 partially inhibited (61 ± 19%, P < .05) the contraction induced only by unactivated PMNs. Moreover, the supernatant from unactivated, but not that from activated, PMNs elicited a contractile response comparable to that from the addition of cells. We observed a significant correlation between the Mac-1/L-selectin ratio of activated PMNs and the contractile response they generated (r = 0.77, P < .05). The activated PMN response had an endothelium-dependent component, whereas the unactivated PMN response was endothelium-independent. These results suggest that human PMNs of varying activation states have the capacity to modulate vascular smooth muscle tone via distinct mechanisms. Unactivated PMNs appear to modulate tone via a secreted product, whereas the more activated phenotype modulates vascular tone via a cognate interaction with the endothelium.