Sulfonated human immunoglobulin enhances CD16-linked CD11b expression on human neutrophils.
Intravenous human immunoglobulin therapy infrequently results in excessive inflammatory responses in vivo; these effects are not fully understood. We assessed whether sulfonated human immunoglobulin (SHIG) or polyethylene glycol-treated human immunoglobulin (PHIG) enhanced expression of inflammatory receptors on peripheral blood neutrophils in vitro, such as alphaMbeta2 (CD11b/CD18) and Fc gamma receptor type III (FcgammaRIII). CD11b and CD16 expression on neutrophils was measured by fluorescence flow cytometry. Various cytokines were assessed using a highly sensitive fluorescence microsphere system. SHIG enhanced/induced CD11b expression and partial aggregations on neutrophils, but PHIG did not. No detection of aggregation IgG was observed in SHIG and PHIG. SHIG-induced CD11b expression was inhibited by treatment of corticosteroid (dexamethasone) and by anti-CD16 monoclonal antibody. Concentrations of various cytokines such as interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, RANTES, tumor necrosis factor (TNF)-alpha, and interferon (INF)-gamma in culture supernatant were not significantly changed by SHIG or PHIG. SHIG and PHIG did not enhance CD16 on neutrophils. SHIG enhanced CD16-linked CD11b expression on neutrophils in vitro. CD11b induction was inhibited by dexamethasone and by anti-CD16 antibody. These in vitro results suggest that aggregations and enhancement of CD11b on neutrophils by SHIG may induce excessive inflammatory responses in vivo.
Kimura
Hirokazu
H
Gunma Prefectural Institute of Public Health and Environmental Sciences, 378, Kamioki, Maebashi, Gunma 371-0052, Japan. kimura-hi@pref.gunma.jp
Kato
Masahiko
M
Ikeda
Miyuki
M
Nagai
Akira
A
Okada
Yasunori
Y
Naito
Shigeto
S
Oshima
Shigeru
S
Taniguchi
Koichi
K
Kozawa
Kunihisa
K
Morikawa
Akihiro
A
D000906:Antibodies / Q000494:pharmacology; D018845:CD11 Antigens / Q000096:biosynthesis / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000009:adverse effects* / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects* / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D017452:Receptors, IgG / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013451:Sulfonic Acids / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000906:Antibodies; D018845:CD11 Antigens; D016207:Cytokines; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG; D013451:Sulfonic Acids; D011092:Polyethylene Glycols; D003907:Dexamethasone