CD18 adhesion receptors, tumor necrosis factor, and neutropenia during septic lung injury.
Sequestration of neutrophils (PMNs) in the pulmonary microvasculature and associated neutropenia are characteristic features of experimental models of septic lung injury. The etiology of altered PMN kinetics during septic lung injury is uncertain, but may be partially due to increased adhesiveness of activated PMNs to pulmonary endothelium. This study examines the relationship between the expression of PMN CD18 adhesion receptors, the evolving neutropenia, and plasma tumor necrosis factor (TNF) activity in a porcine model of septic lung injury. Acute lung injury was induced by infusion of live Pseudomonas aeruginosa (5 x 10(8) CFU/ml at 0.3 ml/20 kg/min) for 60 min (Group Ps, n = 6). Control animals (Group C, n = 3) received a 60-min infusion of sterile 0.9% saline. CD18 expression of circulating PMNs was measured by quantitative immunofluorescent flow cytometry. Plasma TNF activity was measured by L929 fibroblast cytolytic assay. Group Ps developed a significant neutropenia by 30 min (14.9 +/- 2.5 vs 23.4 +/- 3.3 x 10(3) cells/microliter at baseline, P less than 0.05, ANOVA) with circulating neutrophils exhibiting significantly increased CD18 expression by 60 min (6.34 +/- 0.72 vs 5.01 +/- 0.52 equivalent soluble fluorescence molecules (ESFM) x 10(3) at baseline, P less than 0.05, ANOVA). Group Ps demonstrated a significant increase in plasma TNF activity by 30 min (2.5 +/- 0.9 vs 0.7 +/- 0.3 U/ml at baseline). There was no significant change in PMN count, PMN CD18 expression, or plasma TNF activity in Group C. In complimentary in vitro studies, porcine PMNs stimulated with recombinant human TNF-alpha (n = 5) demonstrated a time- and dose-dependent increase in CD18 expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Walsh
C J
CJ
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0519.
Leeper-Woodford
S K
SK
Carey
P D
PD
Cook
D J
DJ
Bechard
D E
DE
Fowler
A A
AA
Sugerman
H J
HJ
D000818:Animals; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D008171:Lung Diseases / Q000473:pathology*; D009503:Neutropenia / Q000209:etiology*; D009504:Neutrophils / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000097:blood* / Q000473:pathology; D011550:Pseudomonas aeruginosa; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016028:Receptors, Leukocyte-Adhesion; D014409:Tumor Necrosis Factor-alpha