Nonleukoreduced red blood cell transfusion induces a sustained inhibition of neutrophil chemotaxis by stimulating in vivo production of transforming growth factor-beta1 by neutrophils: role of the immunoglobulinlike transcript 1, sFasL, and sHLA-I.
BACKGROUND
Red blood cell (RBC) transfusion has been linked to increased susceptibility to infections in critically ill patients and to augmented incidence of postoperative infections. The mechanisms by which transfusions can induce immunosuppression are only partially defined. Recently, it has been demonstrated that RBC supernatants inhibit neutrophil migration. Such inhibitory activity is due to transforming growth factor (TGF)-beta1 contained in the supernatants that desensitize neutrophils to subsequent chemotaxic stimulation.


METHODS
In ancillary experiments, it was observed that plasma from transfused patients maintained its capacity of inhibiting neutrophil chemotaxis several days after RBC transfusion. Thus, this study was planned to investigate the mechanism(s) responsible for the prolonged inhibition of neutrophil chemotaxis observed after RBC transfusion.


RESULTS
Plasma samples obtained from subjects who underwent RBC transfusion display a capability of inhibiting neutrophil chemotaxis, which is detectable up to 15 days after the transfusion. The inhibition is related to the capacity of FasL and HLA-I molecules contained in RBC supernatants to induce in vivo TGF-beta1 synthesis by neutrophils. The induction of TGF-beta1 secretion in neutrophils by HLA-I molecules depends on immunoglobulinlike transcript 1/CD85 triggering.


CONCLUSIONS
The property of RBC transfusion of inducing a sustained inhibition of neutrophil chemotaxis seems to be a potential mechanism that concurs to the susceptibility to infections in patients who receive transfusions. Furthermore, our findings, showing neutrophil production of TGF-beta1 in response to FasL and HLA-I molecules, confirm that neutrophils are endowed not only with effector functions but also with immunomodulatory properties possibly involved in the regulation of inflammatory processes.
Ottonello
Luciano
L
Divisions of Internal Medicine and Clinical Immunology, Department of Internal Medicine, University of Genoa Medical School, Viale Benedetto XV 6, I-16132 Genoa, Italy. otto@unige.it
Ghio
Massimo
M
Contini
Paola
P
Bertolotto
Maria
M
Bianchi
Giordano
G
Montecucco
Fabrizio
F
Colonna
Marco
M
Mazzei
Clemente
C
Dallegri
Franco
F
Indiveri
Franco
F
D015703:Antigens, CD / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D053222:Fas Ligand Protein / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D047589:Leukocyte Reduction Procedures; D009504:Neutrophils / Q000276:immunology*; D011971:Receptors, Immunologic / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
D015703:Antigens, CD; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; D053773:Transforming Growth Factor beta1