A main goal of this project is to determine whether macrophages that are infected with HIV can be activated through the sialophorin (CD43) pathway and whether activation via this pathway contributes in HIV defense. CD43 or sialophorin is a highly glycosylated (60% carbohydrate) cell surface protein found on a number of blood cells, including monocytes/macrophages. We recently found that triggering of CD43 surface molecules with specific mAb initiates activation of human monocytes via a pathway different from the activation pathway of the prototypic monocyte activating agent IFN-gamma. We will characterize the CD43 monocyte activation pathway by investigating whether monocytes that are activated via this pathway have enhanced capability to eliminate infectious agents including Microbacterium avium complex, Pneumocystis carinii, Leishmania donovani, Candida albicans, Legionella pneumophila, as well as human immunodeficiency virus. Other potentially activated properties to be compared in anti-CD43 treated monocytes and control monocytes are: the expression of Class II histocompatibility antigens, the expression of the secreted monokines IL6, TNF-alpha, and IL1-beta, and the expression of the granule-associated cytotoxic peptides that are known collectively as """"""""defensins"""""""". We will also examine whether activation alters the isoform or surface density of CD43 itself. An important goal will be to determine whether the CD43 activation pathway remains wholly or partially functional in HIV-infected monocytes. Finally, we will determine whether CD43 plays a role in the binding and uptake of HIV by monocyte.
| Fratazzi, C; Manjunath, N; Arbeit, R D et al. (2000) A macrophage invasion mechanism for mycobacteria implicating the extracellular domain of CD43. J Exp Med 192:183-92 |
| Fabbi, M; Geginat, J; Tiso, M et al. (1999) 8B4/20, a private CD43 epitope on developing human thymocytes, is involved in thymocyte maturation. J Immunol 163:5964-70 |
| Remold-O'Donnell, E; Parent, D (1995) Specific sensitivity of CD43 to neutrophil elastase. Blood 86:2395-402 |
| Remold-O'Donnell, E; Parent, D (1995) Downregulation of neutrophil CD43 by opsonized zymosan. Blood 85:337-42 |
| Remold-O'Donnell, E; Parent, D (1994) Two proteolytic pathways for down-regulation of the barrier molecule CD43 of human neutrophils. J Immunol 152:3595-605 |
| Schmid, K; Hediger, M A; Brossmer, R et al. (1992) Amino acid sequence of human plasma galactoglycoprotein: identity with the extracellular region of CD43 (sialophorin). Proc Natl Acad Sci U S A 89:663-7 |
