Recruitment of Chlamydia pneumoniae-infected macrophages to the carotid artery wall in noninfected, nonatherosclerotic mice.
OBJECTIVE
Monocyte recruitment into the subendothelium is a crucial step in atherogenesis. Chlamydia pneumoniae resides in circulating monocytes and in the atherosclerotic vascular wall. However, the role of C pneumoniae for monocyte recruitment is unknown. The aim of this study was to examine the impact of C pneumoniae on monocyte adhesion and migration.


RESULTS
C pneumoniae-infected, fluorescence-labeled mouse macrophages (ANA-1) were injected intravenously into noninfected, healthy mice. In vivo videomicroscopy showed increased rolling and firm adhesion to the carotid artery compared with noninfected macrophages. In vitro, C pneumoniae infection (yielding 25% to 35% infected monocytes) increased adhesion of human monocytes or MonoMac6 cells to human umbilical vein endothelial cells and improved cell migration through endothelial-like ECV604 cells. Cell adhesion was inhibited by antibody blockade of very late antigen-4, lymphocyte function-associated antigen-1, macrophage antigen-1, or urokinase receptor, which were found upregulated or activated on C pneumoniae infection (flow cytometry). In contrast, C trachomatis did not induce monocyte adhesion at comparable infection rates (25% to 35%), indicating a unique activation pathway for C pneumoniae. Polymyxin B did not affect C pneumoniae-induced adhesion, excluding a relevant role of lipopolysaccharide in this process.


CONCLUSIONS
These data indicate that C pneumoniae can direct monocytes to predilection sites of nonatherosclerotic vessel walls in vivo by activation of the integrin adhesion receptor system.
May
Andreas E
AE
Deutsches Herzzentrum und 1. Medizinische Klinik, Klinikum Rechts der Isar, Germany. may@dhm.mhn.de
Redecke
Vanessa
V
Grüner
Sabine
S
Schmidt
Roland
R
Massberg
Steffen
S
Miethke
Thomas
T
Ryba
Birgit
B
Prazeres da Costa
Clarissa
C
Schömig
Albert
A
Neumann
Franz-Josef
FJ
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D018821:CD18 Antigens / Q000502:physiology; D017536:Carotid Artery, Common / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D002692:Chlamydia trachomatis / Q000502:physiology; D016993:Chlamydophila pneumoniae / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000502:physiology; D008264:Macrophages / Q000382:microbiology* / Q000473:pathology / Q000637:transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D009928:Organ Specificity; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator
D018821:CD18 Antigens; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator