Activation of the complement system by radiographic contrast media: Studies in vivo and in vitro

Background:Many papers have focused on the importance of granulocytes in the process of reperfusion and ischemia. Most of the clinical studies measured several parameters of this process during and after coronary angiography, without taking into account the effect of the radiographic contrast media (RCM) used during this procedure.Materials and methods:We performed a randomized patient study(n=37)to evaluate the effect of ionic and non-ionic RCM on granulocyte adhesion during coronary angiography. We also evaluated the influence of the ionicity and osmolarity of the different substances on granulocyte adhesion molecules inin vitroexperiments.Results:The osmolarity of patient serum samples increased from 302±1 to 309±1 mOsm/kg(P<0.05)after infusion of RCM. The CD11b expression in the samples of the non-ionic RCM treated group increased from 221±21 MFI to 377±30 MFI(P<0.05)measured as the absolute mean fluorescence intensity (MFI), yet did not alter significantly in the ionic RCM group. In contrast, thein vitroexperiments showed a reduction of the CD11b expression from 360±70 MFI to 149±30 MFI(P<0.05)in the ionic RCM group.Conclusions:The upregulation of adhesion molecules was significantly reducedin vivowith ionic RCM, while ionic substances caused opposite effectsin vitro. This effect should be taken into account when performing leukocyte functional analysis of samples taken during angiography.

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Effect of radiographic contrast media on the complement system in rats

Bulletin of Experimental Biology and Medicine ◽

10.1007/bf00840755 ◽

1989 ◽

Vol 107 (6) ◽

pp. 835-837 ◽

Cited By ~ 3

Author(s):

P. V. Sergeev ◽

A. Ya. Kul'berg ◽

N. L. Shimanovskii ◽

Yu. K. Napolov ◽

S. V. Ukhanov

Keyword(s):

Contrast Media ◽

Complement System ◽

Radiographic Contrast ◽

Radiographic Contrast Media ◽

The Complement System

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Formation of Potential Antigens from Radiographic Contrast Media

Acta Radiologica ◽

10.1177/028418518702800420 ◽

1987 ◽

Vol 28 (4) ◽

pp. 473-477 ◽

Cited By ~ 11

Author(s):

R. Nilsson ◽

L. Ehrenberg ◽

I. Fedorcsak

Keyword(s):

Contrast Media ◽

Serum Proteins ◽

Radical Mechanism ◽

Free Radical Mechanism ◽

Radiographic Contrast ◽

Radiographic Contrast Media ◽

Radiation Induced ◽

Toxic Concentrations

The use of radiographic contrast media is occasionally accompanied by more or less serious adverse effects, evidently of complex etiology, following intravascular administration. Some of these reactions are suspected of having an allergic basis. The in vitro and in vivo formation of iodinated serum proteins following gamma irradiation in the presence of two commonly used radiographic contrast media is demonstrated. Non-toxic concentrations of ascorbate present during the irradiation is shown to prevent the formation of such iodo-proteins in vitro as well as in vivo. The amounts of potentially antigenic iodoprotein formed during radiographic procedures will certainly be very small, but this quantity may be sufficient to elicit a hypersensitivity reaction in cases when an individual has been previously sensitized to immunologically similar iodo-proteins, a mechanism that could account for certain rare and unpredictable reactions. The radiation induced formation of iodo-proteins may also serve as a model for the formation of iodine containing antigens mediated by a free radical mechanism, i.e. in the metabolism of iodinated compounds like erythrosine, a widely used colouring agent for certain foods.

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Anti-GD2 IgA kills tumors by neutrophils without antibody-associated pain in the preclinical treatment of high-risk neuroblastoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-003163 ◽

2021 ◽

Vol 9 (10) ◽

pp. e003163

Author(s):

Mitchell Evers ◽

Marjolein Stip ◽

Kaylee Keller ◽

Hanneke Willemen ◽

Maaike Nederend ◽

...

Keyword(s):

High Risk ◽

Sensory Neurons ◽

Complement System ◽

Severe Pain ◽

Neuroblastoma Cells ◽

Antibody Therapy ◽

Preclinical Treatment ◽

The Complement System

BackgroundThe addition of monoclonal antibody therapy against GD2 to the treatment of high-risk neuroblastoma led to improved responses in patients. Nevertheless, administration of GD2 antibodies against neuroblastoma is associated with therapy-limiting neuropathic pain. This severe pain is evoked at least partially through complement activation on GD2-expressing sensory neurons.MethodsTo reduce pain while maintaining antitumor activity, we have reformatted the approved GD2 antibody ch14.18 into the IgA1 isotype. This novel reformatted IgA is unable to activate the complement system but efficiently activates leukocytes through the FcαRI (CD89).ResultsIgA GD2 did not activate the complement system in vitro nor induced pain in mice. Importantly, neutrophil-mediated killing of neuroblastoma cells is enhanced with IgA in comparison to IgG, resulting in efficient tumoricidal capacity of the antibody in vitro and in vivo.ConclusionsOur results indicate that employing IgA GD2 as a novel isotype has two major benefits: it halts antibody-induced excruciating pain and improves neutrophil-mediated lysis of neuroblastoma. Thus, we postulate that patients with high-risk neuroblastoma would strongly benefit from IgA GD2 therapy.

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Granulocyte Adherence is Inhibited by Radiographic Contrast Media in Vitro

Acta Radiologica ◽

10.1177/028418519203300419 ◽

1992 ◽

Vol 33 (4) ◽

pp. 379-383 ◽

Cited By ~ 9

Author(s):

F. Rasmussen ◽

S. Antonsen ◽

J. Georgsen

Keyword(s):

Contrast Media ◽

Whole Blood ◽

Inhibitory Effect ◽

Significant Inhibition ◽

Autologous Plasma ◽

Radiographic Contrast ◽

Radiographic Contrast Media ◽

Meglumine Diatrizoate ◽

High Concentrations

Different amounts of diatrizoate, ioxaglate, iohexol, iodixanol, NaCl 1000 mOsm/kg, mannitol 1098 mOsm/kg, and meglumine (meglumine concentrations corresponding to the content in the diatrizoate solutions) were added to either whole blood or a suspension of granulocytes in autologous plasma, and the adherence to nylon fibers was determined. At high concentrations all the investigated contrast media (CM) inhibited granulocyte adherence. The degree of inhibition was significantly greater when the ionic CM diatrizoate and ioxaglate were used, as compared with the nonionic media. Meglumine solutions at high concentrations also inhibited adherence but significantly less than diatrizoate solutions containing the same amount of meglumine. Diatrizoate showed the greatest inhibitory effect on granulocyte adherence, and significant inhibition could be detected even with a 1.25% solution.

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