Neutrophil cytoskeletal rearrangements during capillary sequestration in bacterial pneumonia in rats.
BACKGROUND
Neutrophils accumulate in pulmonary capillaries during acute inflammation. Initial events in injury recognition and sequestration do not occur through selectin-mediated rolling. Cytoskeletal rearrangements, as assessed by submembrane F-actin rims, result in poorly deformable neutrophils that may not pass through capillaries.


OBJECTIVE
To test the hypothesis that neutrophils sequestering during pneumonia contain F-actin rims and to determine the roles of CD11/CD18, L-selectin expression, and neutrophil-platelet adhesion in neutrophil sequestration.


METHODS
Neutrophils were compared in blood obtained simultaneously from venous and arterial sites before and 4 h after instillation of Streptococcus pneumoniae or Escherichia coli in rats.


RESULTS
At 4 h of pneumonia, the number of neutrophils was greater in the venous blood entering the lungs than in the arterial blood leaving the lungs, indicating that neutrophil sequestration was occurring. More neutrophils entering the lungs contained F-actin rims than did neutrophils exiting, and the venous-arterial difference in F-actin-rimmed neutrophil counts completely accounted for sequestration. In E. coli pneumonia, in which neutrophil adhesion is mediated by CD11/CD18, CD18 blockade 15 min before blood samples were obtained did not prevent this sequestration of F-actin-rimmed neutrophils. Neutrophils expressing high or low levels of L-selectin or of neutrophils that bound platelets while circulating did not preferentially sequester.


CONCLUSIONS
Neutrophils with cytoskeletal rearrangements preferentially sequester within the lungs during pneumonia, and this sequestration is not due to CD11/CD18-mediated adhesion, L-selectin expression, or platelet adhesion to neutrophils, suggesting that cytoskeletal rearrangements result in sequestration of neutrophils.
Yoshida
Kazuo
K
Division of Integrative Biology, Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.
Kondo
Ryoichi
R
Wang
Qin
Q
Doerschuk
Claire M
CM
D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002196:Capillaries / Q000473:pathology; D002448:Cell Adhesion; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000378:metabolism / Q000473:pathology; D019041:L-Selectin / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D018410:Pneumonia, Bacterial / Q000378:metabolism / Q000473:pathology*; D011018:Pneumonia, Pneumococcal / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew
D000199:Actins; D015415:Biomarkers; D018845:CD11 Antigens; D018821:CD18 Antigens; D019041:L-Selectin