MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA EXPRESSION IN-VIVO AND IN-VITRO - THE ROLE OF LIPOTEICHOIC ACID

Lipoteichoic acid (LTA), a component of the cell wall of most gram-pos itive bacteria, has been shown to play a significant role in the initi ation and progression of bacterial infection. However, little is known of its position in the cytokine network involved in the induction and perpetuation of inflammation. In this study, we assessed whether the macrophage activating and chemotactic cytokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) was expressed in the setting of localiz ed gram-positive infection. Furthermore, we determined whether LTA pur ified from either Staphylococcus aureus or Streptococcus pyogenes coul d induce the expression of MIP-1 alpha mRNA and protein from human blo od monocytes. Immunohistochemical staining of human endocardial sample s obtained from patients with acute S. aureus endocarditis revealed ce ll-associated MIP-1 alpha expression by neutrophils, macrophages, and fibroblasts. Treatment of human peripheral blood monocytes in vitro wi th LTA isolated from either S. aureus or S. pyogenes resulted in both the time- and dose-dependent expression of MIP-1 alpha mRNA. Similarly , staphylococcal and streptococcal LTA induced the dose-dependent prod uction of MIP-1 alpha protein after 24 h in culture. These studies sug gest that LTA may play an important role in triggering the recruitment and activation of leukocytes that characterizes the host response to gram-positive bacterial invasion. (C) 1995 Academic Press, Inc.