Differential activation of alveolar, pulmonary arterial, and systemic arterial neutrophils demonstrates the existence of distinct neutrophil subpopulations in experimental sepsis.
Neutrophils (PMNs) are considered key cellular mediators of sepsis induced acute lung injury. PMN activation is manifest by increased beta 2 integrin expression and enhanced superoxide radical (O2-) generation. What is unclear is at which anatomical sites PMNs are activated and at which sites they release O2- and mediate lung injury. In this study we compared alveolar (ALV), systemic arterial (SA), and pulmonary arterial (PA) PMNs CD18 receptor expression, measured by fluorescent immunophenotyping and, O2- generation, measured by reduction of ferricytochrome C, in septic swine. Swine were anesthetized and ventilated, and given a 1-h infusion of live Pseudomonas aeruginosa. PA, SA, and ALV PMNs were isolated at 0 and 5 h. ALV PMNs O2- was reduced compared to SA blood PMNs O2- at 5 h, (AIV 5 h 23.6 +/- 3 vs. SA 0 h 34.3 +/- 5, p < .05). SA PMNs O2- generation was also significantly reduced compared to PA PMNs at 5 h (PA 5 h 21 +/- 2.5 vs. SA 5 h 16.9 +/- 2.6, p < .05). Alv PMNs expressed significantly greater CD18 receptor levels than SA blood PMNs at 5 h (AIV PMNs 5 h, 76 +/- 6 vs. SA PMNs 5 h 51 +/- 3, p < .05), however, PA PMNs CD18 receptor levels were not significantly different from SA PMNs levels at 5 h. These data corroborate a dissociation between two PMN functions in sepsis. O2- generation was reduced across the lung and following migration. However, alveolar PMNs had significantly upregulated CD18 expression compared to PMNs in PA and SA.(ABSTRACT TRUNCATED AT 250 WORDS)
Windsor
A C
AC
Department of Surgery, Medical College of Virginia-Virginia Commonwealth University, Richmond 23298-0519, USA.
Carey
P D
PD
Sugerman
H J
HJ
Mullen
P G
PG
Walsh
C J
CJ
Fisher
B J
BJ
Blocher
C R
CR
Fowler
A A
AA
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury; D009504:Neutrophils / Q000145:classification / Q000473:pathology / Q000502:physiology*; D011552:Pseudomonas Infections / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000473:pathology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D018805:Sepsis / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D013481:Superoxides / Q000378:metabolism; D013552:Swine
D018821:CD18 Antigens; D013481:Superoxides