title: DAF as a therapeutic target for steroid hormones: implications for host-pathogen interactions.
abstract: In this chapter, we present a concise historic prospective and a summary of accumulated knowledge on steroid hormones, DAF expression, and therapeutic implication of steroid hormone treatment on multiple pathologies, including infection and the host-pathogen interactions. DAF/CD55 plays multiple physiologic functions including tissue protection from the cytotoxic complement injury, an anti-inflammatory function due to its anti-adherence properties which enhance transmigration of monocytes and macrophages and reduce tissue injury. DAF physiologic functions are essential in many organ systems including pregnancy for protection of the semiallogeneic fetus or for preventing uncontrolled infiltration by white cells in their pro- and/or anti-inflammatory functions. DAF expression appears to have multiple regulatory tissue-specific and/or menstrual cycle-specific mechanisms, which involve complex signaling mechanisms. Regulation of DAF expression may involve a direct or an indirect effect of at least the estrogen, progesterone, and corticosteroid regulatory pathways. DAF is exploited in multiple pathologic conditions by pathogens and viruses in chronic tissue infection processes. The binding of Escherichia coli bearing Dr adhesins to the DAF/CD55 receptor is DAF density dependent and triggers internalization of E. coli via an endocytic pathway involving CD55, lipid rafts, and microtubules. Dr+ E. coli or Dr antigen may persist in vivo in the interstitium for several months. Further understanding of such processes should be instrumental in designing therapeutic strategies for multiple conditions involving DAF's protective or pathologic functions and tailoring host expression of DAF.
authors: Department of Obstetrics and Gynecology, Meharry Medical College, 1005 Dr DB Todd Jr. Bulvd, Nashville, TN 37208, USA. bnowicki@mmc.edu
authors: Bogdan
authors: B
authors: Nowicki
authors: Stella
authors: S
authors: Nowicki
mesh_terms: D000328:Adult; D000818:Animals; D018958:CD55 Antigens / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D020249:Hormone Replacement Therapy; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications; D009569:Nitric Oxide / Q000502:physiology; D007752:Obstetric Labor, Premature; D019899:Paracrine Communication / Q000502:physiology; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology; D013256:Steroids / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use*
chemical_list: D018958:CD55 Antigens; D013256:Steroids; D009569:Nitric Oxide; D011374:Progesterone; D003165:Complement System Proteins