Cathepsin G, a neutrophil-derived serine protease, increases susceptibility of macrophages to acute human immunodeficiency virus type 1 infection

Neutrophils dominate acute inflammatory responses that generally evolve int o chronic inflammatory reactions mediated by monocyte/macrophages and lymph ocytes. The latter cell types also serve as major targets for human immunod eficiency virus type 1 (HIV-1). In this study we have investigated the role of neutrophil products, particularly cathepsin G, in AN infection. Catheps in G induced chemotaxis and production of proinflammatory cytokines by macr ophages but not CD4(+) T cells. Pretreatment with cathepsin G markedly incr eased susceptibility of macrophages but not CD4(+) T cells to acute HIV-1 i nfection. When macrophages were exposed to pertussis toxin prior to catheps in G treatment, the cathepsin G-mediated effect was almost abrogated, sugge sting that enhancement of HIV-1 replication by cathepsin G requires Gi prot ein-mediated signal transduction, Although prolonged exposure to cathepsin G suppressed HIV infection of macrophages, serine protease inhibitors, whic h are exuded from the bloodstream later during inflammatory processes, neut ralized the inhibitory effect. Neutrophil extracts or supernatants from neu trophil cultures, which contain cathepsin G, had effects similar to purifie d cathepsin G, Thus, cathepsin G, and possibly other neutrophil-derived ser ine proteases, may have multiple activities in HN-I infection of macrophage s, including chemoattraction of monocyte/macrophage (HIV-1 targets) to infl amed tissue, activation of target cells, and increase in their susceptibili ty to acute HIV-1 infection.