Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production.
Components of the airspace-lining material may contribute to the local regulation of immune function within the lung. We report here that recombinant rat pulmonary surfactant-associated protein D (SP-D) inhibits the lectin- and anti-CD3-stimulated proliferation of human PBMCs. Inhibition was associated with a decreased production of IL-2, and the addition of human rIL-2 blocked the inhibitory action of SP-D. These effects were not inhibited by maltose, indicating that the inhibitory activity was not dependent upon the lectin activity of SP-D. Studies employing mutant SP-D lacking N-linked sugars or defective in multimerization further indicated that inhibition was not dependent upon cellular interactions with the N-linked oligosaccharide on SP-D or the oligomerization of trimeric SP-D subunits. Although a peptide containing an inverted DGR showed similar IL-2-dependent effects on anti-CD3-stimulated proliferation, deletion of the conserved DGRDGR sequence near the amino-terminal end of the collagen domain did not decrease the suppressive activity of SP-D. We hypothesize that SP-D can dampen lymphocyte responses to exogenous stimuli and protect the lung against collateral immune-mediated damage.
Borron
P J
PJ
Department of Medicine, The Lawson Research Institute, St. Joseph's Health Centre, The University of Western Ontario, London, Canada. p.borron@cellbio.duke.edu
Crouch
E C
EC
Lewis
J F
JF
Wright
J R
JR
Possmayer
F
F
Fraher
L J
LJ
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006023:Glycoproteins / Q000235:genetics / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008320:Maltose / Q000494:pharmacology; D008969:Molecular Sequence Data; D016853:Muromonab-CD3 / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D010835:Phytohemagglutinins / Q000494:pharmacology; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D006023:Glycoproteins; D006131:Growth Inhibitors; D007376:Interleukin-2; D016853:Muromonab-CD3; D010835:Phytohemagglutinins; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011993:Recombinant Fusion Proteins; D003208:Concanavalin A; D008320:Maltose