In vivo impairment of neutrophil recruitment during lentivirus infection.
Evidence indicates that the lentivirus, HIV, infection affects neutrophil response to bacteria and bacterial products in vitro. We used a novel model of rapid onset immunosuppression following infection with a similar lentivirus, feline immunodeficiency virus (FIV), in cats to examine neutrophil function within the microvasculature in vivo and to determine the steps that are impaired in the neutrophil recruitment cascade. In uninfected cats and cats infected neonatally with FIV, the mesentery was exteriorized, but remained autoperfused during intravital microscopy for 4 h. When the tissue was superfused with 10 micro g/ml of LPS for 4 h, intravital microscopy displayed a profound increase in neutrophil rolling at both 8 and 12 wk of age in uninfected cats. At 12 wk of age, FIV-infected animals showed a profound decrease in the number of rolling neutrophils. In vitro studies revealed that neutrophils from infected and uninfected animals rolled equally well on surrogate selectin substrata. In addition, in vivo neutrophil adhesion and emigration out of the vasculature were severely reduced, and in vitro neutrophil chemotaxis from FIV-infected animals was significantly impaired in response to fMLP or IL-8. However, FIV infection of neutrophils could not be detected. In summary, in vivo lentivirus infection with immunosuppression leads to a severe impairment in neutrophil rolling, adhesion, and emigration in response to bacterial stimulants potentially involving both endothelial and neutrophil dysfunction. These in vivo studies also indicate that neutrophil dysfunction should be taken into account when treating infections and tissue injury.
Department of Physiology and Biophysics, University of Calgary, Alberta, Canada. pkubes@ucalgary.ca
Paul
P
Kubes
Bryan
B
Heit
Guido
G
van Marle
James B
JB
Johnston
Derrice
D
Knight
Adil
A
Khan
Christopher
C
Power
D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000276:immunology; D002415:Cats; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D016089:Immunodeficiency Virus, Feline / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load
D008070:Lipopolysaccharides