Role of human neutrophil peptides in the initial interaction between lung epithelial cells and CD4+ lymphocytes.
Human neutrophil peptides (HNP) exert immune-modulating effects. We hypothesized that HNP link innate and adaptive immunity through activation of costimulatory molecules. Human lung epithelial cells and CD4+ lymphocytes were treated with HNP separately or in coculture. Stimulation with HNP induced an increase in cell surface expression of CD54 (ICAM-1), CD80, and CD86 on lung epithelial cells and the corresponding major ligands, CD11a (LFA-1), CD152 (CTLA-4), and CD28 on CD4+ lymphocytes. There was an increased nuclear expression of the transcription factor p53 in human alveolar A549 cells and an elevated NF-kappaB (p50) and a degradation of I-kappaB protein in CD4+ lymphocytes following HNP stimulation. HNP enhanced the interaction between A549 cells and CD4+ lymphocytes by increasing cell adhesion and release of IFN-gamma, IL-2, and IL-8. This was attenuated by using an alpha1-proteinase inhibitor to neutralize HNP. We conclude that HNP play an important role in linking innate to acquired immunity by activation of costimulatory molecules in lung epithelial cells and CD4+ lymphocytes.
Vaschetto
Rosanna
R
Department of Anaesthesia, University of Toronto, St. Michael's Hospital, Room 7-007, Queen Wing, 30 Bond St., Toronto, ON M5B 1W8, Canada.
Grinstein
Jonathan
J
Del Sorbo
Lorenzo
L
Khine
Aye Aye
AA
Voglis
Stefanos
S
Tullis
Elizabeth
E
Slutsky
Arthur S
AS
Zhang
Haibo
H
D000890:Anti-Infective Agents / Q000494:pharmacology; D000954:Antigens, Surface / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D002448:Cell Adhesion; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007109:Immunity; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023084:alpha-Defensins / Q000494:pharmacology*
D000890:Anti-Infective Agents; D000954:Antigens, Surface; D020672:I-kappa B Proteins; D007376:Interleukin-2; D016209:Interleukin-8; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D023084:alpha-Defensins; D007371:Interferon-gamma