Suppression of cytokine-mediated beta2-integrin activation on circulating neutrophils in critically ill patients.
The beta2 integrin CD11b plays a central role in inflammation and the systemic inflammatory response syndrome (SIRS). The CD11b molecule activates in two ways: the density of membrane-bound CD11b up-regulates and the molecule undergoes a conformational change that confers adhesiveness to counter-receptors. We studied the kinetics of CD11b activation in patients with SIRS. We found a significantly diminished CD11b activation in response to tumor necrosis factor alpha (TNF-alpha). This affected all circulating polymorphonuclear neutrophils (PMN) and was an intrinsic property of the cells and not due to antagonism by soluble TNF-alpha receptors or loss of cellular receptors for TNF-alpha. Diminished responsiveness correlated with the severity of organ failure and lasted for months in some patients but had no impact on mortality. We speculate that reduced CD11b responsiveness in SIRS contributes to the high risk of recurrent infection, but that it may also be protective against excessive PMN activation within the vascular space.
Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania, USA. ajr3+@pitt.edu
A J
AJ
Rosenbloom
M R
MR
Pinsky
C
C
Napolitano
T S
TS
Nguyen
D
D
Levann
N
N
Pencosky
A
A
Dorrance
B K
BK
Ray
T
T
Whiteside
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018821:CD18 Antigens / Q000097:blood / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000276:immunology; D006801:Humans; D016177:Macrophage-1 Antigen / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha