Lipopolysaccharide induces intracytoplasmic migration of the polymorphonuclear leukocyte CD11b/CD18 receptor.
We investigated the effects of lipopolysaccharide (LPS) on the subcellular location of the integrin receptor CD11b/CD18 (Mac-1). Cytoplast and subcellular fractionation experiments were performed to distinguish between receptor shedding and intracellular receptor transport as mechanisms involved for the effects of LPS on CD11b/CD18 expression. Cytoplast preparations demonstrated the same percentage of cell-associated receptors +/- LPS. Subcellular fractionation experiments demonstrated a shift from primarily plasma membrane fractions to azurophilic granules. Protein tyrosine kinase inhibition with genistein (50 microM) inhibited the LPS-induced translocation of CD11b/CD18 receptors to azurophilic granules. The effects of LPS (10 ng/mL) alone were reproduced with LPS (.1 ng/mL) plus heat-inactivated pooled normal human serum. Preincubation of PMN with anti-CD14 monoclonal antibodies prevented the effects of LPS+serum on the translocation of CD11b/CD18 receptors. These results demonstrate that LPS regulates CD11b/CD18 expression by inducing intracytoplasmic translocation of this receptor to azurophilic granules. This process involves activation of protein tyrosine kinase, and endosomal acidification contributes to the degradation of these receptors within azurophilic granules.
Simms
H H
HH
Department of Surgery, Brown University School of Medicine, Rhode Island Hospital, Providence 02903, USA.
D'Amico
R
R
D000209:Acute-Phase Proteins; D000818:Animals; D018845:CD11 Antigens / Q000187:drug effects; D002352:Carrier Proteins / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry; D002465:Cell Movement; D002467:Cell Nucleus; D003593:Cytoplasm / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins; D051379:Mice; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D018845:CD11 Antigens; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; D000099231:Lipopolysaccharide-Binding Protein