HIV-1 envelope gp41 peptides promote migration of human Fc epsilon RI+ cells and inhibit IL-13 synthesis through interaction with formyl peptide receptors.
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.
de Paulis
Amato
A
Division of Clinical Immunology and Allergy, University of Naples Federico II, Via Sergio Pansini 5, 80131 Naples, Italy.
Florio
Giovanni
G
Prevete
Nella
N
Triggiani
Massimo
M
Fiorentino
Isabella
I
Genovese
Arturo
A
Marone
Gianni
G
D000328:Adult; D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001491:Basophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D044042:Receptors, Formyl Peptide; D017455:Receptors, IgE / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000502:physiology*; D018000:Receptors, Peptide / Q000502:physiology*
D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; D015700:HIV Envelope Protein gp41; D018793:Interleukin-13; D010446:Peptide Fragments; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016572:Cyclosporine; C050025:cyclosporin H