Interaction of HIV-1 gp120 molecule fragments with human monocytes: different requirements for tumor necrosis factor-alpha and IL-6 production.
The HIV-1 gp120 recombinant protein fragment encompassing aa residues 410-511, that contains the CD4 binding region (rp120cd), and fragment aa 446-511, which lacks the sequence responsible for CD4 binding (rp120), were synthesized to study their ability to induce TNF synthesis in human monocytes. The rp120cd stimulated TNF alpha secretion by monocytes while the rp120 and full-length recombinant protein (FL gp120), used as control, failed to do so. However, FL gp120 stimulated peripheral blood mononuclear cells (PBMC) and lymphocytes for TNF production and this was inhibited by anti-CD4 MAb. The rp120cd also caused TNF secretion by PBMC that was not blocked by this antibody. Furthermore, FL gp120 but not rp120cd inhibited anti-CD4 mAb binding to CEM cells. Hence, FL gp120 may cause TNF release from lymphocytes by binding to CD4, while rp120cd interacts with monocytes but not lymphocytes and induces TNF production by a mechanism not involving CD4 binding. Unexpectedly, FL gp120 but not rp120cd stimulated IL-6 secretion and IL-6 mRNA synthesis in monocytes. The FL gp120-induced production of IL-6 by monocytes was inhibited by anti-CD4 monoclonal antibody (MAb). Thus, there may be different requirements for TNF induction in lymphocytes and monocytes stimulated with various preparations of gp120 and for the selective induction of cytokines in monocytes. The enhanced production of TNF in HIV infection and AIDS may involve distinct cellular sources and different mechanisms.
Zembala
M
M
Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow.
Pryjma
J
J
Plucienniczak
A
A
Szczepanek
A
A
Jasinski
M
M
Ruggiero
I
I
Piselli
P
P
Colizzi
V
V
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015850:Interleukin-6; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha