Submandibular salivary proteases: lack of a role in anti-HIV activity.
Whole human saliva contains a number of proteolytic enzymes, mostly derived from white blood cells and bacteria in the oral cavity. However, less information is available regarding proteases produced by salivary glands and present in salivary secretions. In the present study, we have analyzed submandibular saliva, collected without contaminating cells, and identified multiple proteolytic activities. These have been characterized in terms of their susceptibility to a series of protease inhibitors. The submandibular saliva proteases were shown to be sensitive to both serine and acidic protease inhibitors. We also used protease inhibitors to determine if salivary proteolytic activity was involved in the inhibition of HIV infectivity seen when the virus is incubated with human saliva. This anti-HIV activity has been reported to occur in whole saliva and in ductal saliva obtained from both the parotid and submandibular glands, with highest levels of activity present in the latter fluid. Protease inhibitors, at concentrations sufficient to block salivary proteolytic activity in an in vitro infectivity assay, did not block the anti-HIV effects of saliva, suggesting that the salivary proteases are not responsible for the inhibition of HIV-1 infectivity.
Kennedy
S
S
Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104-6003, USA.
Davis
C
C
Abrams
W R
WR
Billings
P C
PC
Nagashunmugam
T
T
Friedman
H
H
Malamud
D
D
D019380:Anti-HIV Agents / Q000494:pharmacology*; D007611:Aprotinin / Q000494:pharmacology; D001550:Benzamidines / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D010450:Endopeptidases / Q000494:pharmacology*; D005033:Ethylmaleimide / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D009646:Norleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D010306:Parotid Gland / Q000201:enzymology / Q000378:metabolism; D010436:Pepstatins / Q000494:pharmacology; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D012463:Saliva / Q000201:enzymology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013363:Submandibular Gland / Q000201:enzymology* / Q000378:metabolism; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology
D019380:Anti-HIV Agents; D001550:Benzamidines; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D010436:Pepstatins; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; C014195:Streptomyces pepsin inhibitor; D007531:Isoflurophate; D004533:Egtazic Acid; D010664:Phenylmethylsulfonyl Fluoride; C000909:N-diazoacetylnorleucine methyl ester; D009646:Norleucine; D007611:Aprotinin; D004492:Edetic Acid; D010450:Endopeptidases; D008666:Metalloendopeptidases; C032854:leupeptin; C032157:benzamidine; D005033:Ethylmaleimide; C031375:pepstatin