Changes in polymorphonuclear leukocyte surface and plasma bactericidal/permeability-increasing protein and plasma lipopolysaccharide binding protein during endotoxemia or sepsis.
OBJECTIVE
To evaluate changes in levels of polymorphonuclear leukocyte surface bactericidal/permeability-increasing protein (BPI), plasma BPI, and plasma lipopolysaccharide (LPS) binding protein (LBP) in normal human volunteers administered Escherichia coli LPS and in patients with sepsis and gram-negative infections.


METHODS
Survey; case series.


METHODS
Clinical research center and surgical intensive care unit of a medical school and an associated tertiary care hospital.


METHODS
Volunteers (n = 10) screened prior to study by history and physical examination to exclude those with underlying diseases or hematologic abnormalities. Consecutive sample of surgical intensive care unit patients (n = 10) meeting criteria for sepsis syndrome with gram-negative infection. An additional patient with systemic inflammatory response syndrome but no gram-negative infection. All patients were studied on meeting the criteria. Three of the patients with sepsis syndrome and the patient with systemic inflammatory response syndrome were evaluated on recovery (approximately 25 days after initial study). Because these studies in volunteers and patients overlapped temporally, the control values were those of volunteers evaluated prior to LPS administration. No matching was employed.


RESULTS
Compared with controls, LPS-challenged volunteers and patients with sepsis both exhibited significant granulocytosis (P < .01) and increased concentrations of polymorphonuclear leukocyte surface BPI (P < .01) and of plasma LBP (P < .01). Plasma BPI concentrations were increased (P < .01) in volunteers following LPS administration. There was a trend toward increased concentrations of plasma BPI in patients, but this was not significant relative to controls. Maximum concentrations of plasma LBP were approximately 250- and 3000-fold higher than plasma BPI concentrations in endotoxemic volunteers and in patients, respectively.


CONCLUSIONS
Circulating polymorphonuclear leukocytes increase expression of BPI in response to LPS or gram-negative sepsis. Subsequently, concentrations of plasma BPI and LBP increase. Because both LBP and BPI bind to LPS, it is suggested that endogenously derived plasma levels of BPI are likely to be inadequate to compete for LPS binding to the much more abundant LBP in the circulation.
Calvano
S E
SE
Surgical Immunology Laboratory, New York Hospital, Cornell University Medical College, New York.
Thompson
W A
WA
Marra
M N
MN
Coyle
S M
SM
de Riesthal
H F
HF
Trousdale
R K
RK
Barie
P S
PS
Scott
R W
RW
Moldawer
L L
LL
Lowry
S F
SF
D000209:Acute-Phase Proteins / Q000032:analysis*; D000328:Adult; D023181:Antimicrobial Cationic Peptides; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000032:analysis* / Q000737:chemistry*; D002352:Carrier Proteins / Q000097:blood*; D004731:Endotoxins / Q000009:adverse effects / Q000097:blood*; D004926:Escherichia coli; D016905:Gram-Negative Bacterial Infections / Q000097:blood*; D006801:Humans; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009504:Neutrophils / Q000737:chemistry* / Q000473:pathology; D011446:Prospective Studies; D015996:Survival Rate; D013577:Syndrome; D013997:Time Factors; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D004731:Endotoxins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000099231:Lipopolysaccharide-Binding Protein; C021623:bactericidal permeability increasing protein