Endothehal cell activation 1s Important m the pathogenesls of preeclampsla, however, the nature of the actlvatlon IS unknown We investigated 22 patients with preeclampsla, 29 normotensive pregnancies, and 18 nonpregnant women to test the hypothesis that serum from preeclamptlc patients induces expresslon of mtercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-l (VCAM-1) and stimulates mtracellular free calcium concentrations [Ca"], m cultured endothehal cells We then asked whether the correspondmg mtegrm adhesive counter receptors lymphocyte function-associated antigen-1 (CDlla/CD18), macrophage-1 antigen (CDllb/CD18), p150,95 (CD1 1 c/CD18), and very late actlvatlon antigen-4 (CD49/CD29) are Increased m patients with preeclampsla In the pregnant women, the measurements were conducted both before and after delivery Integrm expression was measured by fluorescent antibody cell sorting analysis using monoclonal antibodies ICAMand VCAM-1 were analyzed on endothehal cells by enzymelinked lmmunosorbent assay [Ca2+], was measured with fura 2 Serum from preeclamptlc patients increased endothehal cell ICAM-expresslon but not VCAM-1 expresslon Preeclamptlc I ntact endothehal cells have antiadhesive and antlcoagulant properties, regulate vascular permeability, and modulate the effect of vasoconstrlctor agomsts on the vessel wall 1 Several lmes of evidence support the hypothesis that dysfunction of the vascular endothelmm is important m the pathogenesis of preeclampsla 2-4 The vascular response to vasoconstrictors in preeclamptic women 1s greatly enhanced, the tendency for coagulation is increased,5-* the capillaries are more permeable,6*9-11 and the plasma concentrations of endothelm and fibronectm are elevated I*-** Glomerular capillary endothehal cells show charactenstlc signs of endothehal cell dysfunction.22 Indirect evidence suggests that endothelial cell leukocyte adhesion 1s also altered m preeclampsla, however, neither expression of endothehal cell adhesion molecules nor the leukocyte counterreceptor mtegrins have been investigatedEndothehal cell leukocyte adhesion IS medlated by four classes of adhesion molecules, the selectms, carbohydrate-contammg selectm hgands, mtegrms, and immunoglobulm-like (Ig-like) molecules.23 The mteractlon between mtegrms on the surface of leukocytes and Ig-hke molecules on endothelium 1s necessary for stable adhe- The four integrins that appear most important in leukocyte-endothelial adhesion are three p2 mtegnns, each with a different (Y subunit, and one pl mtegrin. The @l mtegrin is the VLA-4 mtegrin, also termed a4pl according to the integrin nomenclature, or CD49/CD29 according to the CD nomenclature. The three p2 mtegrms share the p2 chain (CD18) and are named LFA-1, also termed (uLp1 or CD1 la/CD18; MAC-l, also termed aMP2 or CD1 lb/CD18; and the glycoprotein p150,95, also termed (~Xp2 or CDllc/CD18.Evidence exists for an as yet umdentlfied circulatmg factor which 1s released from the hypoxlc placenta into the maternal clrculatlon m preeclampsla. This...
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