Vasoactive agents modulate migration of monocytes across glomerular endothelial cells

Background: Macrophages seem to play an important role in the development o f glomerulosclerosis. In both human and experimental animal models of focal glomerulosclerosis (FSGS), infiltration of macrophages in the mesangium ha s been considered key in the development of FSGS, Methods: In the present study, we evaluated the effect of vasoactive agents on the migration of monocytes across a filter in a modified Boyden chamber as well as across a cultured glomerular endothelial cell layer (in vitro m odel of glomerular mesangium). Both light as well as scanning electron micr oscopic studies were performed. We evaluated the effect of vasoactive agent s including histamine, prostaglandin (PG) E-2, angiotensin II, endothelin-1 , platelet-activating factor, and interleukin-1 (IL) an the migration of mo nocytes/macrophages across an endothelial cell layer as well as a gelatin-c oated filter, In addition, we evaluated the effect of cyclic adenosine 3',5 ' cyclic monophosphate (cAMP) and PGE(2) on vasoactive-induced migration of monocytes. Results: Histamine increased (P<0.003) the migration of monocytes across th e filter. This effect of histamine mas dose-dependent. Histamine at concent rations of 10(-8) to 10(-5) mol/L induced optimal migration across the filt er (control, 16.6+/-1.1 vs histamine, 10(-8) mol/L, 40.9+/-0.9 monocytes/hi gh power field), Cimetidine, an H-2 receptor blocker, attenuated (P<0.001) the effect of histamine on the migration of monocytes, PGE(2) inhibited the migration of monocytes in a dose dependent manner. Histamine increased (P< 0.001) the passage of monocytes across the glomerular endothelial cell laye r (control, 1012+/-37 vs 1711+/-163 cpm/well), Histamine also increased the migration of murine macrophages across the glomerular endothelial cell lay er, PGE(2) inhibited the migration of monocytes across the endothelial cell layer under basal as well as histamine-stimulated states, Dibutyryl cyclic (DBc) AMP also attenuated the migration of monocytes under basal as well a s histamine-stimulated states, Both PGE(2) and DBcAMP also attenuated the I L-1 beta-stimulated migration of monocytes. Angiotensin II, endothelin-1, a nd platelet-activating factor did not modulate the migration of monocytes, Conclusions: Vasoactive agents directly modulate the transmigration of mono cytes, The present in vitro study provides a basis for a hypothesis that va soactive agents may also be modulating the migration of monocytes across th e glomerular endothelial cell layer (into the mesangium).