Effects of candidate vaginally-applied microbicide compounds on innate immune cells.
Ideally, a vaginally-applied microbicide would be effective against a broad range of pathogens but would have minimal effects on the female genital tract. The aim of this study was to determine if representative candidate detergent-type and sulfated/sulfonated polymer-type microbicides altered the composition or function of innate immune cells normally found in the vaginal mucosa. The effect of microbicide on the composition of vaginal leukocytes was tested using a flow cytometric approach. Application of the detergent cholic acid, but not the sulfated polysaccharide lambda carrageenan, resulted in a significant increase in macrophages at the vaginal epithelial surface compared to control treatment (19.3% macrophages compared to 2.8%; p<0.0004). Phagocytosis of fluorochrome-labeled bacteria by macrophages was inhibited greater than 50% in the presence of 1.0mg/ml of the sulfonated polymer PRO 2000 but was not inhibited by the same concentration of lambda carrageenan. PRO 2000-pulsed macrophages regained phagocytic function after being washed free of the compound. Culture of macrophages with PRO 2000 also resulted in diminished detection of the surface proteins CD11b and CD18. After treated cells were washed free of PRO 2000, these proteins were detected at levels similar to control treated cells. In conclusion, application of a detergent-type microbicide, but not a sulfated polymer, resulted in the infiltration of inflammatory cells at the vaginal epithelial surface. Phagocytic function of macrophages was lost in the presence of 1mg/ml PRO 2000 which may have reflected masking of important cell surface proteins by the microbicide; however, there was no evidence of permanent loss of function upon removal of the compound.
Milligan
Gregg N
GN
Sealy Center for Vaccine Development, 301 University Boulevard, Galveston, TX 77555-0436, USA. gnmillig@utmb.edu
Young
Christal G
CG
Meador
Michael G
MG
Chu
Chin-Fun
CF
Stanberry
Lawrence R
LR
D000282:Administration, Intravaginal; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000633:toxicity*; D002351:Carrageenan / Q000008:administration & dosage / Q000633:toxicity; D019826:Cholic Acid / Q000008:administration & dosage / Q000633:toxicity; D003902:Detergents / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D009092:Mucous Membrane / Q000166:cytology / Q000382:microbiology; D009282:Naphthalenesulfonates / Q000008:administration & dosage / Q000633:toxicity; D010587:Phagocytosis / Q000187:drug effects; D011108:Polymers / Q000008:administration & dosage / Q000633:toxicity; D011137:Polystyrenes / Q000008:administration & dosage / Q000633:toxicity; D014621:Vagina / Q000166:cytology / Q000276:immunology* / Q000382:microbiology
D000891:Anti-Infective Agents, Local; D003902:Detergents; D009282:Naphthalenesulfonates; C120231:PRO 2000; D011108:Polymers; D011137:Polystyrenes; C003321:polystyrene sulfonic acid; D002351:Carrageenan; D019826:Cholic Acid