HIV-1 envelope gp41 peptides promote migration of human Fc epsilon RI+ cells and inhibit IL-13 synthesis through interaction with formyl peptide receptors

• Published in: The Journal of immunology (1950) Vol. 169; no. 8; pp. 4559 - 4567
• Main Authors: de Paulis, Amato, Florio, Giovanni, Prevete, Nella, Triggiani, Massimo, Fiorentino, Isabella, Genovese, Arturo, Marone, Gianni
• Format: Journal Article
• Language: English
• Published: United States 15.10.2002
• Subjects: Adult; Amino Acid Sequence; Antibodies, Anti-Idiotypic - pharmacology; Basophils - cytology; Basophils - drug effects; Basophils - immunology; Basophils - metabolism; Chemotaxis, Leukocyte - drug effects; Chemotaxis, Leukocyte - immunology; Cyclosporine - pharmacology; Cytokines - metabolism; Histamine Release - drug effects; Histamine Release - immunology; HIV Envelope Protein gp41 - pharmacology; Humans; Immunoglobulin E - immunology; Interleukin-13 - antagonists & inhibitors; Interleukin-13 - biosynthesis; Interleukin-13 - genetics; Interleukin-13 - metabolism; Molecular Sequence Data; N-Formylmethionine Leucyl-Phenylalanine - metabolism; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Peptide Fragments - chemical synthesis; Peptide Fragments - pharmacology; Receptors, Formyl Peptide; Receptors, IgE - biosynthesis; Receptors, Immunologic - physiology; Receptors, Peptide - physiology; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.8.4559

We evaluated the effects of synthetic peptides (2017, 2019, 2020, 2021, 2023, 2027, 2029, 2030, 2031, and 2035) encompassing the structure of HIV-1(MN) envelope gp41 on both chemotaxis of human basophils and the release of preformed mediators (histamine) and of cytokines (IL-13). Peptides 2019 and 2021 were potent basophil chemoattractants, whereas the other peptides examined were ineffective. Preincubation of basophils with FMLP or gp41 2019 resulted in complete desensitization to a subsequent challenge with homologous stimulus. Incubation of basophils with low concentration (5 x 10(-7) M) of FMLP, which binds with high affinity to N-formyl peptide receptor (FPR), but not to FPR-like 1, did not affect the chemotactic response to a heterologous stimulus (gp41 2019). In contrast, a high concentration (10(-4) M) of FMLP, which binds also to FPR-like 1, significantly reduced the chemotactic response to gp41 2019. The FPR antagonist cyclosporin H inhibited chemotaxis induced by FMLP, but not by gp41 2019. None of these peptides singly induced the release of histamine or cytokines (IL-4 and IL-13) from basophils. However, low concentrations of peptides 2019 and 2021 (10(-8)-10(-6) M) inhibited histamine release from basophils challenged with FMLP but not the secretion caused by anti-IgE and gp120. Preincubation of basophils with peptides 2019 and 2021 inhibited the expression of both IL-13 mRNA, and the FMLP-induced release of IL-13 from basophils. These data highlight the complexity of the interactions between viral and bacterial peptides with FPR subtypes on human basophils.