Specific surface proteins of Neisseria meningitidis have been proposed to 
stimulate leukocytes during tissue invasion and septic shock. In this study, we 
demonstrate that the adhesin N. meningitidis Adhesin A (NadA) involved in the 
colonization of the respiratory epithelium by hypervirulent N. meningitidis B 
strains also binds to and activates human monocytes/macrophages. Expression of 
NadA on the surface on Escherichia coli does not increase bacterial-monocyte 
association, but a NadA-positive strain induced a significantly higher amount of 
TNF-alpha and IL-8 compared with the parental NadA-negative strain, suggesting 
that NadA has an intrinsic stimulatory action on these cells. Consistently, 
highly pure, soluble NadA(Delta351-405), a proposed component of an 
antimeningococcal vaccine, efficiently stimulates monocytes/macrophages to 
secrete a selected pattern of cytokines and chemotactic factors characterized by 
high levels of IL-8, IL-6, MCP-1, and MIP-1alpha and low levels of the main 
vasoactive mediators TNF-alpha and IL-1. NadA(Delta351-405) also inhibited 
monocyte apoptosis and determined its differentiation into a macrophage-like 
phenotype.