Effect of recombinant secretory leukocyte protease inhibitor on hiv infection in human macrophages


Nejat Düzgüneş: 0000-0001-6159-1391


Biomedical Sciences

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FASEB Journal







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Secretory leukocyte protease inhibitor (SLPI) inhibits a range of serine proteases including neutrophil elastase (NE), cathepsin G, trypsin, and chymotrypsin. The major physiological role of SLPI is thought to be the protection of the mucosal epithelium against excessive proteolytic activity. Several studies have also shown that recombinant SLPI can inhibit HIV infection of macrophages and primary T-cells. Further studies have shown that rSLPI does not interact with the HIV aspartyl protease or reverse transcriptase but most likely binds to a host cell-surface molecule other than the primary HIV-1 receptor, CD4. Interestingly, several cell-surface serine proteases have been identified as possible complementary factors for HIV-1 infection. The purpose of our study was to determine whether there is a correlation between the anti-HIV and the serine protease inhibitory activities of rSLPI. Anti-HIV activity was monitored by measurement of p24 production by macrophages infected with HIV-lBaL in the presence of rSLPI. We found that the C-terminal (Asn55-Alal07) domain of SLPI, which contains the serine protease inhibitory site and which has an inhibitory capacity as strong as the full-length SLPI against NE, cathepsin G, and chymotrypsin, had no HIV inhibitory effect. Also, rSLPI samples containing increasim" amounts of oxidized methionyl residues retained similar abilities to inhibit HIV-1 infection of macrophages. Oxidation of the methionyl residues of SLPI decreases the affinity of SLPI for both chymotrypsin and trypsin. These data suggest that the serine protease inhibitory activity of SLPI may not be important for inhibition of HIV-1 infection of macrophages by SLPI. This work was supported by Pacific Dental Research Foundation grants 504 and 505.

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