Affiliations: [a] Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia | [b] Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel | [c] Department of Gastroenterology, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Correspondence:
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Corresponding author: Yehuda Shoenfeld, Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel Hashomer, 52621, Israel. Tel.: +972 3 530 2652; Fax: +972 3 535 2855; E-mail:[email protected]
Abstract: INTRODUCTION: Intravenous immunoglobulin (IVIG) has been widely
used to treat various conditions, including inflammatory and autoimmune
diseases. IVIG has been shown to have a direct influence on neutrophils,
eosinophils and lymphocytes. However, many aspects IVIG's effect on
neutrophils activation still remain unknown. OBJECTIVE: To evaluate the effect of IVIG on PMA-induced activation
of neutrophils, with and without priming with TNF-α, in a series of
in vitro experiments performed on whole blood. RESULTS: Our data coincided with well-known literature indicating
that the effect of phorbol 12-myristate 13-acetate (PMA) on human leukocytes
includes activation of neutrophils, monocytes and eosinophils, increase of
chemiluminescence (CL) and induction of netosis, resulting in assembly of
traps. In presence of IVIG (10 mg/mL), CL was reduced by 25% in response
to PMA compared to PMA-induced leukocyte activation without IVIG. Decreasing
IVIG concentration to 1 mg/mL and below did not inhibit PMA-induced
activation of CL.PMA-induced activation after TNF-α priming resulted in approximately
50% increase of amplitude of CL response to PMA. Moreover, maximum CL was
reached by minute 5, which was more rapid than in the absence of TNF-α-priming
(in this case maximum CL was reached by minute 15).The IVIG concentrations did not affect morphological changes of leukocytes
after sequential addition of TNF-α and PMA. IVIG had no effect on
leukocyte content and on PMA-induced CL of primed leukocytes.Addition of IVIG under TNF-α priming significantly increased the
number of traps in the smears in response to PMA activation. Of note, such
an increase in the number of traps was depended on the IVIG concentration in
plasma. CONCLUSION: In conclusion, we suggest that IVIG is able to reduce
the degradation of traps under priming with TNF-α. Moreover, IVIG
might switch the activation of primed leukocytes to netosis.
