MESANGIAL CELL-DERIVED TRANSFORMING GROWTH-FACTOR-BETA-1 REDUCES MACROPHAGE ADHESIVENESS WITH CONSEQUENT DEACTIVATION

Adhesion of macrophages is a crucial event that determines the number and function of macrophages at inflammatory sites. The aim of this stu dy was to elucidate the role of mesangial cells in the regulation of m acrophage adhesiveness. J774.2 macrophages were suspended in serial di lutions of mesangial cell conditioned medium (MC medium) and seeded on plastic tissue Culture plates. MC medium did not affect the initial a dhesion of macrophages but induced subsequent detachment in a concentr ation-dependent manner. A similar effect was observed when macrophages were plated on plastic coated with laminin, collagen type IV or Matri gel. The reduced adhesiveness was reversible, and cell viability was u naffected by MC medium, indicating that the effect is not due to cytot oxicity. Conditioned media from fibroblastic, epithelial and endotheli al cell lines did not induce macrophage detachment. To identify the ac tive component in MC medium, we examined the involvement of transformi ng growth factor-beta 1 (TGF-beta 1) in the process. Mesangial cells c onstitutively expressed TGF-beta 1 mRNA, and MC medium contained the a ctive form of TGF-beta 1. Exogenously added TGF-beta 1 induced macroph age detachment in a dose dependent manner, and an anti-TGF-beta 1 neut ralizing antibody partially abolished the activity of MC medium, indic ating the involvement of TGF-beta 1 as an active component. Compared t o adherent cells, detached macrophages showed reduced mitogenic activi ty and blunted induction of IL-1 beta and IL-6 in response to lipopoly saccharide. These data demonstrate that TGF-beta 1 is a mesangial cell -derived factor that impairs adhesiveness of macrophages and confers b lunted responses to a specific stimulus. These findings suggest one po tential mechanism for macrophage clearance from inflamed glomeruli.