Pulmonary surfactant proteins A and D directly suppress CD3+/CD4+ cell function: evidence for two shared mechanisms.
Pulmonary surfactant is a lipoprotein complex that lowers surface tension at the air-liquid interface of the lung and participates in pulmonary host defense. Surfactant proteins (SP), SP-A and SP-D, modulate a variety of immune cell functions, including the production of cytokines and free radicals. Previous studies showed that SP-A and SP-D inhibit lymphocyte proliferation in the presence of accessory cells. The goal of this study was to determine whether SP-A and SP-D directly suppress Th cell function. Both proteins inhibited CD3(+)/CD4(+) lymphocyte proliferation induced by PMA and ionomycin in an IL-2-independent manner. Both proteins decreased the number of cells entering the S and mitotic phases of the cell cycle. Neither SP-A nor SP-D altered cell viability, apoptosis, or secretion of IL-2, IL-4, or IFN-gamma when Th cells were treated with PMA and ionomycin. However, both proteins attenuated ionomycin-induced cytosolic free calcium ([Ca(2+) ](i)), but not thapsigargin-induced changes in [Ca(2+)](i). In summary, inhibition of T cell proliferation by SP-A and SP-D occurs via two mechanisms, an IL-2-dependent mechanism observed with accessory cell-dependent T cell mitogens and specific Ag, as well as an IL-2-independent mechanism of suppression that potentially involves attenuation of [Ca(2+)](i).
Borron
Paul J
PJ
Departments of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Mostaghel
Elahe A
EA
Doyle
Carolyn
C
Walsh
Eric S
ES
McHeyzer-Williams
Michael G
MG
Wright
Jo Rae
JR
D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D015759:Ionomycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D037662:Pulmonary Surfactant-Associated Protein A / Q000494:pharmacology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000494:pharmacology*; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D017252:CD3 Complex; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D015759:Ionomycin; D019284:Thapsigargin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium