Luminescence studies of the phagocyte response to endotoxin infusion into normal human subjects: multiple discriminant analysis of luminescence response and correlation with phagocyte morphologic changes and release of elastase.
A blood luminescence system (BLS) was employed to analyze blood phagocyte function in response to infusion of endotoxin (4 ng Escherichia coli lipopolysaccharide (LPS)/kg body weight) into 7 healthy human subjects. The subjects were closely monitored clinically, and extensive chemical, hematological and coagulation measurements were taken during the pretreatment, early (symptomatic, 1-8 h post-LPS), and late (asymptomatic, 12-48 h post-LPS) phases of acute inflammation. BLS assessment included measurement of basal and PMA-stimulated phagocyte oxidase and myeloperoxidase (MPO) activities, and also included measurement of circulating (COR) and PAF-primed maximum (MOR) opsonin receptor-dependent phagocytic activities. Basal oxidase activity peaked at T + 1 h and showed an additional peak at T + 24 h post-LPS. The COR activity also peaked at 1-2 h, but remained elevated through T + 24 h post-LPS, while the basal MPO activity peaked only once at T + 1 h. We concluded that while MPO evidence of phagocyte respiratory activation returned to baseline by T + 4 h, COR evidence of receptor expression (receptor alert) remained elevated through T + 24 h. During this early (0-8 h) period, elastase/alpha 1AT complex concentration peaked at T + 3-4 h and again at T + 8 h. Peak numbers of circulating polarized and vacuolated phagocytes also appeared at T + 3 h and 7 h. We concluded that there was biochemical and morphological evidence of continuing phagocyte activity beyond T + 4 h to T + 8 h, and that this corresponded with the period during which the subjects were symptomatic. In addition, the appearance of a second peak of basal oxidase activity at T + 24 h, multiple discriminant analyses of all the luminescence data, and the sustained elevation of lactate suggested that there was a later second stage (T + 12 h to 48 h) of the human response to endotoxin, during which time the subjects were asymptomatic.
Taylor
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F
Cardiovascular Biology Research, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA. Marie-Brewer@omrf.ouhsc.edu
Haddad
P A
PA
Kinasewitz
G
G
Chang
A
A
Peer
G
G
Allen
R C
RC
D000328:Adult; D016002:Discriminant Analysis; D004731:Endotoxins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008163:Luminescent Measurements; D008297:Male; D009895:Opsonin Proteins / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010586:Phagocytes / Q000201:enzymology / Q000502:physiology*; D011971:Receptors, Immunologic / Q000378:metabolism
D004731:Endotoxins; D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D011971:Receptors, Immunologic; D010088:Oxidoreductases; D009195:Peroxidase; D010196:Pancreatic Elastase