title: Increased surface expression of CD11b/c and CD18 appears to be dissociated from anti-CD11b/c monoclonal antibody stimulated O2- anion generation in in vivo Escherichia coli lipopolysaccharide and tumor necrosis factor-alpha-treated rat neutrophils.
abstract: The purpose of this investigation was to determine the effect of anti-rat CD11b/c monoclonal antibody (MAb) on in vitro superoxide anion (O2-) generation in in vivo Escherichia coli lipopolysaccharide (LPS) and tumor necrosis-alpha (TNF)-treated rat polymorphonuclear leukocytes (PMN). After a continuous infusion of a nonlethal dose of E. coli LPS (.5 mg/kg) or TNF (6.0 x 10(5) units) into rats, PMN were recovered by centrifugal elutriation and discontinuous density gradient centrifugation from the liver (LPS-treated) and whole blood (LPS- and TNF-treated) and compared for CD11b/c, CD11a, and CD18 upregulation and their capacity for basal and agonist-stimulated O2- production. Immunofluorescence flow cytometry studies of rat whole blood PMN demonstrated that, upon LPS infusion, there was a time-dependent upregulation of CD11b/c and CD18, but not of CD11a. Similarly, TNF infusion upregulated CD11b/c although to a lesser degree. Stimulation of LPS- and TNF-treated PMN with phorbol 12-myristate 13-acetate (PMA), opsonized zymosan (OPZ), and anti-rat CD11b/c MAb triggered O2- generation. Although total O2- generated by OPZ and anti-rat CD11b/c MAb was less than that generated by PMA stimulation, the in vivo LPS- and TNF-induced beta 2 integrin upregulation did not result in a statistically significant enhancement of O2- generation with respect to normal saline-treated PMN. Our results do not appear to support the hypothesis that enhanced expression of CD11b/c or CD18 might be associated with enhanced in vitro anti-CD11b/c MAb-triggered O2- generation in LPS- and TNF-treated PMN in vivo.
authors.affiliation: Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Mayer
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: J A
authors.initials: JA
authors.lastname: Spitzer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018845:CD11 Antigens / Q000096:biosynthesis* / Q000276:immunology; D018821:CD18 Antigens / Q000096:biosynthesis* / Q000276:immunology; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology; D004926:Escherichia coli; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000145:classification / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000502:physiology; D008297:Male; D015999:Multivariate Analysis; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate