IL-16 regulation of human mast cells/basophils and their susceptibility to HIV-1.
AIDS patients often contain HIV-1-infected mast cells (MCs)/basophils in their peripheral blood, and in vivo-differentiated MCs/basophils have been isolated from the blood of asthma patients that are HIV-1 susceptible ex vivo due to their surface expression of CD4 and varied chemokine receptors. Because IL-16 is a ligand for CD4 and/or an undefined CD4-associated protein, the ability of this multifunctional cytokine to regulate the development of human MCs/basophils from nongranulated progenitors residing in cord or peripheral blood was evaluated. After 3 wk of culture in the presence of c-kit ligand, IL-16 induced the progenitors residing in the blood of normal individuals to increase their expression of chymase and tryptase about 20-fold. As assessed immunohistochemically, >80% of these tryptase(+) and/or chymase(+) cells expressed CD4. The resulting cells responded to IL-16 in an in vitro chemotaxis assay, and this biologic response could be blocked by anti-IL-16 and anti-CD4 Abs as well as by a competitive peptide inhibitor corresponding to a sequence in the C-terminal domain of IL-16. The additional finding that IL-16 induces calcium mobilization in the HMC-1 cell line indicates that IL-16 acts directly on MCs and their committed progenitors. IL-16-treated MCs/basophils also are less susceptible to infection by an M/R5-tropic strain of HIV-1. Thus, IL-16 regulates MCs/basophils at a number of levels, including their vulnerability to retroviral infection.
Qi
Jian Cheng
JC
Department of Medicine, University of New South Wales, Australia.
Stevens
Richard L
RL
Wadley
Robert
R
Collins
Andrew
A
Cooley
Margaret
M
Naif
Hassan M
HM
Nasr
Najla
N
Cunningham
Anthony
A
Katsoulotos
Gregory
G
Wanigasek
Yewlan
Y
Roufogalis
Basil
B
Krilis
Steven A
SA
D000998:Antiviral Agents / Q000502:physiology; D001491:Basophils / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D019410:Interleukin-16 / Q000097:blood / Q000502:physiology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000276:immunology
D000998:Antiviral Agents; D019410:Interleukin-16; D002118:Calcium