CXC chemokines Gro(alpha)/IL-8 and IP-10/MIG in Helicobacter pylori gastritis.
Infection with Helicobacter pylori causes chronic active gastritis, which is characterized by neutrophils infiltrating the gastric epithelial layer and the underlying lamina propria as well as by T, B lymphocytes and macrophages accumulating in the lamina propria. In this study, the chemokine profile responsible for the recruitment of these inflammatory cells is investigated. Using both RNA/RNA in situ hybridization and immunohistochemistry, the expression of the neutrophil and/or lymphocyte-attractant CXC chemokines growth-related oncogene alpha (Gro(alpha)), IL-8, interferon-gamma (IFN-gamma)-inducible protein-10 (IP-10), monokine induced by IFN-gamma (MIG) and the CC chemokines macrophage inflammatory protein-1alpha (MIP-1alpha), -1beta, regulated on activation normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1) is studied and microanatomically localized in the gastric mucosa. Macrophages in the lamina propria at sites with neutrophil infiltration and gastric epithelium infiltrated by neutrophils highly expressed the neutrophil-attractant chemokines Gro(alpha) and IL-8. Additionally, Gro(alpha) and IL-8 were expressed by neutrophils themselves localized within gastric epithelium, in the foveolar lumen and in the cellular debris overlying mucosal erosion. IP-10 and to a lower extent MIG, both selectively chemotactic for inflammatory T cells, were expressed by endothelial cells of gastric mucosal vessels and by mononuclear cells at sites with T cell infiltration. Expression of all other CC chemokines tested was significantly lower. These in vivo data indicate that a set of predominantly CXC chemokines modulates the inflammation in H. pylori gastritis. Gro(alpha) and IL-8 may play an important role in neutrophil trafficking from the mucosal vessel into the gastric epithelium, whereas IP-10 and MIG contribute to the recruitment of inflammatory T cells into the mucosa.
Eck
M
M
Institut für Pathologie, Universität Würzburg, Germany. Matth.Eck@gmx.de
Schmausser
B
B
Scheller
K
K
Toksoy
A
A
Kraus
M
M
Menzel
T
T
Müller-Hermelink
H K
HK
Gillitzer
R
R
D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism*; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism; D005753:Gastric Mucosa / Q000276:immunology / Q000473:pathology; D005756:Gastritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
C475829:CXCL1 protein, human; C080810:CXCL9 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger