Monocyte chemoattractant protein-1 production by intestinal myofibroblasts in response to staphylococcal enterotoxin a: relevance to staphylococcal enterotoxigenic disease.
Food poisoning due to staphylococcal enterotoxins A and B (SEA and SEB) affects hundreds of thousands of people annually. SEA and SEB induce massive intestinal cytokine production, which is believed to be the key factor in staphylococcal enterotoxin enteropathy. MHC class II molecules are the major receptors for staphylococcal enterotoxins. We recently demonstrated that normal human subepithelial intestinal myofibroblasts (IMFs) express MHC class II molecules. We hypothesized that IMFs are among the first cells to respond to staphylococcal enterotoxins and contribute to the cytokine production associated with staphylococcal enterotoxin pathogenesis. We demonstrated here that primary cultured IMFs bind staphylococcal enterotoxins in a MHC class II-dependent fashion in vitro. We also demonstrated that staphylococcal enterotoxins can cross a CaCo-2 epithelial monolayer in coculture with IMFs and bind to the MHC class II on IMFs. IMFs responded to SEA, but not SEB, exposure with 3- to 20-fold increases in the production of proinflammatory chemokines (MCP-1, IL-8), cytokines (IL-6), and growth factors (GM-CSF and G-CSF). The SEA induction of the proinflammatory mediators by IMFs resulted from the efficient cross-linking of MHC class II molecules because cross-linking of class II MHC by biotinylated anti-HLA-DR Abs induced similar cytokine patterns. The studies presented here show that MCP-1 is central to the production of other cytokines elicited by SEA in IMFs because its neutralization with specific Abs prevented the expression of IL-6 and IL-8 by IMFs. Thus, MCP-1 may play a leading role in initiation of inflammatory injury associated with staphylococcal enterotoxigenic disease.
Pinchuk
Irina V
IV
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
Beswick
Ellen J
EJ
Saada
Jamal I
JI
Suarez
Giovanni
G
Winston
John
J
Mifflin
Randy C
RC
Di Mari
John F
JF
Powell
Don W
DW
Reyes
Victor E
VE
D000906:Antibodies / Q000276:immunology; D019921:Biotinylation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007422:Intestines / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D032446:Myoblasts / Q000187:drug effects / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*
D000906:Antibodies; D018932:Chemokine CCL2; D016207:Cytokines; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal