Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome.
OBJECTIVE
A hallmark of sepsis and severe systemic inflammatory response syndrome (SIRS) is the massive recruitment of immature neutrophils from the bone marrow into the circulation (left shift, band forms). Their capacity to participate in innate defense against bacteria is ill defined. We aimed at comparing various innate immune functions of mature vs. immature neutrophils circulating during sepsis and SIRS.


METHODS
Prospective, observational cohort study.


METHODS
Tertiary level ICU and associated research laboratory.


METHODS
: Thirty-three ICU patients with sepsis; 12 ICUs with SIRS; 32 healthy volunteers.


METHODS
Twenty milliliters of whole heparinized blood was used for in vitro studies including neutrophil viability and apoptosis, surface expression of CD16, Toll-like receptors () 4 and TLR2, CD14, MD-2, HLA-DP,-DQ and -DR, and CXCR2, chemotaxis, phagocytosis, bacterial killing, and tumor necrosis factor-α/interleukin-10 baseline intracellular cytokine levels.


RESULTS
Immature neutrophils were capable of mediating important innate immune functions such as bacterial phagocytosis and killing via the production of reactive oxygen species, although less efficiently than mature neutrophils. Immature neutrophils had a longer life span and resistance to spontaneous apoptosis, and could mature ex vivo. They expressed lower levels of receptors for bacterial molecules such as CD14 and MD-2 and migrated less efficiently than mature granulocytes. Immature neutrophils had higher basal intracellular tumor necrosis factor-α/interleukin-10 ratio than that of mature neutrophils, suggesting a proinflammatory phenotype. No significant differences were observed between immature neutrophils isolated from patients with sepsis and those from patients with severe SIRS.


CONCLUSIONS
Despite their "immaturity", band forms are capable of mediating crucial innate immune functions during severe infections and sepsis. Their fate and capacity to mature in vivo remain to be determined.
Laboratory of Intensive Care, University Hospitals of Geneva, University of Geneva, Switzerland.
Geneviève
G
Drifte
Irène
I
Dunn-Siegrist
Pierre
P
Tissières
Jérôme
J
Pugin
D000368:Aged; D000369:Aged, 80 and over; D001770:Blood Bactericidal Activity; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000150:complications / Q000276:immunology*; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha