Altered neutrophil trafficking during sepsis.
In sepsis, dysregulation of the inflammatory system is well known, as reflected in excessive inflammatory mediator production, complement activation, and appearance of defects in phagocytic cells. In the current study sepsis was induced in rats by cecal ligation/puncture. Early in sepsis the beta(1) and beta(2) integrin content on blood neutrophils increased in a nontranscriptional manner, and the increase in beta(2), but not beta(1), integrin content was C5a dependent. Similar changes could be induced in vitro on blood neutrophils following contact with phorbol ester or C5a. Direct injury of lungs of normal rats induced by deposition of IgG immune complexes (IgG-IC) caused 5-fold increases in the myeloperoxidase content that was beta(2), but not beta(1), dependent. In contrast, in cecal ligation/puncture lungs myeloperoxidase increased 10-fold after IgG immune complex deposition and was both beta(1) and beta(2) integrin dependent. These data suggest that sepsis causes enhanced neutrophil trafficking into the lung via mechanisms that are not engaged in the nonseptic state.
Guo
Ren-Feng
RF
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Riedemann
Niels C
NC
Laudes
Ines J
IJ
Sarma
Vidya J
VJ
Kunkel
Robin G
RG
Dilley
Kari A
KA
Paulauskis
Joseph D
JD
Ward
Peter A
PA
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018821:CD18 Antigens / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000008:administration & dosage; D007262:Infusions, Intravenous; D019012:Integrin beta1 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D008026:Ligation; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011677:Punctures; D051381:Rats; D020318:Rats, Long-Evans; D018805:Sepsis / Q000097:blood / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018821:CD18 Antigens; D005353:Fibronectins; D007074:Immunoglobulin G; D019012:Integrin beta1; D015936:Complement C5a; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate