Interactions between HIV-infected monocytes and the extracellular matrix: HIV-infected monocytes secrete neutral metalloproteases that degrade basement membrane protein matrices

• Published in: Journal of leukocyte biology 1992-08, Vol.52 (2), p.244-248
• Main Authors: Dhawan, Subhash, Toro, Luis A., Jones, B. Eric, Meltzer, Monte S.
• Format: Article
• Language: English
• Subjects: basement membrane; Basement Membrane - metabolism; Biological and medical sciences; Cells, Cultured; extracellular matrix; Extracellular Matrix Proteins - metabolism; Fundamental and applied biological sciences. Psychology; HIV - pathogenicity; HIV‐1; human immunodeficiency virus; Humans; Metalloendopeptidases - physiology; metalloprotease; Microbiology; Monocytes - metabolism; Monocytes - microbiology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Virology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.52.2.244

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 < 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.