LPS activation of Toll-like receptor 4 signals CD11b/CD18 expression in neutrophils.
We identify herein a novel signaling function of the Toll-like receptor-4 (TLR4), the lipopolysaccharide (LPS) receptor mediating the innate immune response, in inducing the expression of CD11b/CD18 integrin in polymorphonuclear leukocytes (PMNs). Studies were made in PMNs isolated from TLR4-deficient (TLR4(-/-)) and C57BL/6 [wild-type (WT)] mice. We observed increased CD11b expression in WT PMNs within 3 h after LPS challenge, whereas CD11b was not expressed in TLR4(-/-) PMNs above basal levels. TLR4-activated CD11b expression was cycloheximide sensitive and involved the activation of transcription factors, NF-kappaB and c-Jun/PU.1. TLR4(-/-) PMNs challenged with LPS were functionally defective as the result of the impaired CD11b expression in that they failed to adhere and did not migrate across endothelial cells in response to N-formylmethionyl-leucyl-phenylalanine. TLR4 also promoted increased binding of LPS to PMNs on the basis of expression of CD11b. Thus TLR4 signaling activates synthesis and upregulation of CD11b and is essential for PMN adhesion and transmigration. Our data suggest an important role of TLR4-activated CD11b expression in the mechanism of the PMN host-defense response to LPS.
Zhou
Ximing
X
Department of Pharmacology, College of Medicine, University of Illinois, 835 So. Wolcott Ave., Chicago, IL 60612, USA. ximingz@uic.edu
Gao
Xiao-Pei
XP
Fan
Jie
J
Liu
Qinghui
Q
Anwar
Khandaker N
KN
Frey
Randall S
RS
Malik
Asrar B
AB
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015534:Trans-Activators / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
D039481:CD11b Antigen; D018821:CD18 Antigens; D003513:Cycloheximide; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1