Pneumocystis carinii major surface glycoprotein induces interleukin-8 and monocyte chemoattractant protein-1 release from a human alveolar epithelial cell line.
BACKGROUND
The major surface glycoprotein (MSG) is an abundant, immunogenic glycoprotein located on the surface of Pneumocystis carinii. Little is known about the proinflammatory effects of MSG.


METHODS
We have investigated the effect of human MSG on the secretion of the chemokines interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) from an alveolar epithelial cell line (A549).


RESULTS
Incubation of A549 cells with MSG in concentrations from 0.4 to 10 microg mL-1 for 24 h caused dose-dependent increases in IL-8 release (3.4-fold above control, P < 0.01). Time course experiments showed increases in IL-8 release at 4 h, 8 h and 24 h compared with control cultures (all P < 0.01). There was a minor (13%) dose- and time-related increase in MCP-1 release at 24 h (P = 0.02). Co-incubation of MSG with mannan or beta-glucan decreased IL-8 release by 48% and 42% respectively, suggesting that MSG stimulates A549 cells in part through carbohydrate moieties. Dexamethasone significantly inhibited MSG-induced IL-8 release in concentrations of 10-6-10-8 mol L-1 compared with control experiments (P < 0.01). Ribonuclease protection assays for steady-state IL-8 mRNA showed that increases in response to MSG stimulation occurred by 4 h and persisted throughout 8 h of stimulation.


CONCLUSIONS
These findings suggest that MSG can alter alveolar epithelial cytokine release and may be capable of modulating the local inflammatory response in this manner.
Benfield
T L
TL
University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark. tbenfield@inet.uni2.dk
Lundgren
B
B
Shelhamer
J H
JH
Lundgren
J D
JD
D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000276:immunology; D005656:Fungal Proteins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D005936:Glucans / Q000008:administration & dosage; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008351:Mannans / Q000008:administration & dosage; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D011010:Pneumocystis / Q000276:immunology / Q000472:pathogenicity*; D011650:Pulmonary Alveoli / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D018932:Chemokine CCL2; D005656:Fungal Proteins; D005936:Glucans; D005938:Glucocorticoids; D016209:Interleukin-8; D008351:Mannans; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C077556:GPA protein, Pneumocystis carinii sp.; D003907:Dexamethasone