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.
Gunma Prefectural Institute of Public Health and Environmental Sciences, 378, Kamioki, Maebashi, Gunma 371-0052, Japan. kimura-hi@pref.gunma.jp
Hirokazu
H
Kimura
Masahiko
M
Kato
Miyuki
M
Ikeda
Akira
A
Nagai
Yasunori
Y
Okada
Shigeto
S
Naito
Shigeru
S
Oshima
Koichi
K
Taniguchi
Kunihisa
K
Kozawa
Akihiro
A
Morikawa
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