Interactions between HIV-infected monocytes and the extracellular matrix: HIV-infected monocytes secrete neutral metalloproteases that degrade basement membrane protein matrices.
The frequency of human immunodeficiency virus (HIV)-infected monocytes that spread on a model basement membrane was about twofold greater than that of an equal number of uninfected control cells through the initial 12 to 18 h of culture. By 24 h, virtually all HIV-infected and uninfected control cells spread on the basement membrane gel. The frequency of spread cells in the uninfected control population was less than 10% of total cells by 12 days. In contrast, 30 to 40% of HIV-infected monocytes remained spread through this time interval and formed a dense interdigitated network of cell processes on and into the gel matrix. Invasion of the basement membrane matrix by HIV-infected monocytes suggested increased secretion of proteases able to digest the gel. Indeed, levels of neutral protease activity in culture fluids from HIV-infected monocytes were significantly higher than those from equal numbers of uninfected control cells. High levels of protease activity in culture fluids of HIV-infected monocytes required productive virus infection and were not observed with cells exposed to T cell-tropic HIV isolates. The predominant protease activity in these cultures was a 92-kd neutral metallogelatinase. HIV-induced changes in monocyte metalloprotease activity may be important for extravasation of infected cells to tissue or for the development of AIDS-associated neuropathology, carcinogenesis, and opportunistic infection.
Dhawan
S
S
Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC.
Toro
L A
LA
Jones
B E
BE
Meltzer
M S
MS
D001485:Basement Membrane / Q000378:metabolism; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006678:HIV / Q000472:pathogenicity*; D006801:Humans; D008666:Metalloendopeptidases / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology*
D016326:Extracellular Matrix Proteins; D008666:Metalloendopeptidases